Review Open Access
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Sep 15, 2023; 15(9): 1505-1519
Published online Sep 15, 2023. doi: 10.4251/wjgo.v15.i9.1505
Deoxyribonucleic acid methylation driven aberrations in pancreatic cancer-related pathways
Akash Bararia, Nilabja Sikdar, Human Genetics Unit, Indian Statistical Institute, Kolkata 700108, India
Amlan Das, Department of Biochemistry, Royal Global University, Assam 781035, India
Sangeeta Mitra, Department of Biochemistry and Biophysics, University of Kalyani, West Bengal 741235, India
Sudeep Banerjee, Department of Gastrointestinal Surgery, Tata Medical Center, Kolkata 700160, India
Aniruddha Chatterjee, Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin 9054, New Zealand
Aniruddha Chatterjee, School of Health Sciences and Technology, University of Petroleum and Energy Studies, Dehradun 248007, India
ORCID number: Akash Bararia (0000-0002-9069-3116); Amlan Das (0000-0002-9295-3743); Sangeeta Mitra (0000-0002-0651-2280); Sudeep Banerjee (0000-0002-3157-4184); Aniruddha Chatterjee (0000-0001-7276-2248); Nilabja Sikdar (0000-0003-4465-472X).
Author contributions: Bararia A, Das A, and Mitra S wrote the first draft of the paper and constructed the flow chart and tables; Chatterjee A, Banerjee S, and Sikdar N provided valuable input, suggestions, comments and guidance while writing the review manuscript and contributed to proofreading and editing; Sikdar N constructed, conceptualized, and edited the review manuscript.
Supported by the Department of Biotechnology, Government of India Grant Sanction, Ramalingaswami Re-entry Fellowship, No. RLS/BT/Re-entry/05/2012.
Conflict-of-interest statement: All the authors declare no conflicts of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Nilabja Sikdar, PhD, Research Scientist, Doctor, Human Genetics Unit, Indian Statistical Institute, 203, B.T. Road, Kolkata 700108, India.
Received: April 18, 2023
Peer-review started: April 18, 2023
First decision: May 12, 2023
Revised: May 29, 2023
Accepted: August 1, 2023
Article in press: August 1, 2023
Published online: September 15, 2023


Pancreatic cancer (PanCa) presents a catastrophic disease with poor overall survival at advanced stages, with immediate requirement of new and effective treatment options. Besides genetic mutations, epigenetic dysregulation of signaling pathway-associated enriched genes are considered as novel therapeutic target. Mechanisms beneath the deoxyribonucleic acid methylation and its utility in developing of epi-drugs in PanCa are under trails. Combinations of epigenetic medicines with conventional cytotoxic treatments or targeted therapy are promising options to improving the dismal response and survival rate of PanCa patients. Recent studies have identified potentially valid pathways that support the prediction that future PanCa clinical trials will include vigorous testing of epigenomic therapies. Epigenetics thus promises to generate a significant amount of new knowledge of biological and medical importance. Our review could identify various components of epigenetic mechanisms known to be involved in the initiation and development of pancreatic ductal adenocarcinoma and related precancerous lesions, and novel pharmacological strategies that target these components could potentially lead to breakthroughs. We aim to highlight the possibilities that exist and the potential therapeutic interventions.

Key Words: Methylation driven pathways, Pancreatic cancer methylation markers, Signaling pathway targeted therapy, PanCa enriched methylated pathway, Pre-cancer methylated pathways

Core Tip: Given the limited commercial availability of targeted epi-drugs and pathway-based biomarkers, it is important to generalize them for appropriate treatment of pancreatic cancer and related precancerous lesions. We also highlighted the clinical use of these therapeutic targets based on methylation driven pathways. This review will successfully help readers address current issues and support cutting-edge development of targeted therapies using epigenetically regulated pathways.


Pancreatic cancer (PanCa) is one of the fatal malicious carcinomas globally. Currently, PanCa is one of the foremost causes of death by cancer especially in the United States[1]. According to GLOBACON 2020, PanCa is the 12th most common cause of cancer with 495000 new cases worldwide, of which approximately 47% of new cases occurred in Asia and another significant proportion, 28%, in Europe[2]. By the end of 2022, the incidence could increase by 70%, equivalent to about 844000 new cases per year[3]. Recent studies elucidate deoxyribonucleic acid (DNA) methylation depiction from inflammatory diseases thus opening a new profile for the biomarker development in early prognosis. Cell-free DNA methylation, in particular, could be used to identify pre-neoplastic features in individuals with suspected pancreatic disorders. This is a clear non-invasive approach of PanCa pre-diagnosis[4]. It is observed through the years that PanCa consists of extremely fatal malignancies, having less than 5 year of survival rate. Early detection and treatment of this disease is hampered due to a lack of reliable diagnostic and prognostic markers[3]. It has been noted that there is epigenetic variance between populations which can be accounted for by a variety of racial, demographic, and vocational characteristics. Only a few research have examined the Pancreatic ductal Adenocarcinoma (PDAC) progression stage globally and the shifting epigenetic landscape in various ethnic groups[5]. Recent research has demonstrated the dynamic changes in the global DNA methylation and gene expression patterns play important roles in cancer development, including PanCa development. These findings offer important new information for understanding the onset and progression of this malignancy[5].

PanCa is clinically allied with an elevated rate of mortality. In terms of geographic features, Northern America and Europe show the maximum prevalence of PanCa where more males tend to get affected. There are an estimated 62210 (male) and 32970 (female) new cases in the United States alone in 2022, with an estimated 25970 male and 23860 PanCa-related deaths[2,3]. In South Eastern countries like India, the rate of incidence of PanCa are comparatively lower compared to the Western world. According to per year statistics in Eastern countries like in India, the rate of prevalence of PanCa seems to be 0.5 to 2.4 out of 100000 women and 0.2 to 1.8 out of 100000 men. Although, regardless of the prevalence of this deadly disease, patient survivability with PanCa is comparatively downcast with 1 to 5-year of relative survival rates for all stages[6]. The main reason for such miserable and prolonged consequences is perhaps because of the fact that this fatal disease is predominantly lacks any symptoms in the early stages. Meanwhile, the symptoms commence to expand largely and eventually tend to get metastatic in nature[7]. As a result, enucleating a metastatic tumor is frequently impossible. PanCa has a 1-year survival rate of 26%, and the 5-year survival rate is roughly 6% for advanced cancer and 22% for early stages when surgical removal of the tumor is still possible[8]. For this reason, few new therapeutic strategies like radiotherapy and chemotherapy are effective to mitigate the tumor size in selected PanCa patients[9]. Hypermethylation in DNA methylation can promote tumorigenesis. However, with histone and RNA methylation, both writers and erasers can be PanCa oncogenes such as SMYD3, KDM1, MELLT3 and FTO[10].

The study of malignant genomic modifications has been ongoing over the past few decades, and it has become quite evident that epigenetics are crucial to carcinogenesis. DNA methylation, a key component of epigenetics, affects a variety of biological functions, including gene imprinting, genome stability, and cell differentiation. Hypermethylation and hypomethylation are the two categories of abnormal DNA methylation. DNA hypomethylation refers to less DNA methylation, which frequently causes disturbance of chromosome stability or increased aneuploidy. On the other hand, DNA hypermethylation refers to the buildup of methylation, which mostly results in transcriptional repression and reduced gene expression. Typically, abnormal DNA methylation can be seen in the promoter regions of transcription factors, which promotes the growth and metastasis of cancers[11,12]. DNA methylation plays a crucial role in the onset and progression of cancer. Early on in the tumorigenic process, DNA methylation alterations frequently take place. This phenomenon has been confirmed for the bladder, lung, breast, colorectal, and pancreatic pre-neoplastic lesions[13,14].

According to Thompson et al[15], 2015, out of around 250000 assessed CpG sites, 20000 hotspots were correlated with patient survival. The two categories that were survival (-) and survival (+) which represented the connection between higher methylation and survival. The survival (+) sites were more evenly dispersed intragenically, whereas the survival (-) sites tended to group close to the TSS (transcription start site), indicating hypermethylation of promoter regions. An increased methylation pattern, associated with shorter survival was observed in survival (-) groups, while reduced methylation led to longer survival times in survival (+) groups. Some of the important genes [within the top 10 in survival (-) groups] which were found to be hypermethylated were FAM150A, ONECUT1, RASSF10, RNF207, PanCa DH9. The tumor-suppressor role of these genes are well-established in other aggressive cancers. While the genes such as PTPRN2, MAD1L1, CBFA2T3, COL5A1, and SHANK2 etc. made their way into the top ten differentially methylated genes in the survival (+) group[16]. Thus, this segmentation, together with the fact that promoter regions of genes are typically better defined and documented, led to the surviving sites producing a clearer recovery of functional annotation and genes overall[17]. There is growing evidence that DNA methylation can affect how genes are expressed, despite the fact that the majority of research on DNA methylation has focused on the methylation state of promoters and CpG islands. Importantly, a mutation of KRAS in acinar or ductal cells causes the development of pancreatic lesions, which is the causative genetic event in over 90% of PDAC cases (PanIN). Along with the KRAS mutation, subsequent deletion mutations or mutations of other types in tumor suppressor genes promote tumor growth and accelerate the course of the disease[10,18].

The Advantageous incidence of this systematic review is to summarize all the differential methylation pathways in several precancerous lesions of PanCa. The alterations in epigenetics occurring in PanCa also discussed in this review. This review also gives insight into landscapes of the early epigenetics in precursor lesions. In this review also highlighted the differentially methylated enriched signaling pathways and methylated modulators, and their therapeutic targets for precancerous as well as PanCa. In brief, we describe an overview of differentially methylated genes, highlighting their diagnostic or prognostic potential in PanCa related enriched pathways (Figure 1).

Figure 1
Figure 1 Comprehensive visualization showcasing interaction between epigenetic pathways and probable drug treatments concerning pancreatic cancer. EGF: Epidermal growth factor; Ras/Raf/MEK/ERK: Rat sarcoma virus/Rapidly Accelerated Fibrosarcoma/Mitogen-activated protein kinase/extracellular-signal-regulated kinase; PI3K/AKT/mTOR: Phosphoinositide 3-kinases/Ak strain transforming/Mammalian target of rapamycin; Wnt: Wingless-related integration site; PDGF: Platelet-derived growth factor; SCF/c-Kit: Stem cell factor/receptor tyrosine kinase; ALK: Anaplastic lymphoma kinase; TGF-β: Transforming growth factor beta; HGF: Hepatocyte growth factor; JAK/STAT: Janus kinase/signal transducers and activators of transcription; BTK: Bruton tyrosine kinase; Src: Tyrosine-protein kinase (sarcoma); COX-2: Cyclooxygenase 2; NRF2: Nuclear factor erythroid 2–related factor 2; HIF-1: Hypoxia-inducible factor-1; PKCδ-PKD1: Protein Kinase Cδ-Polycystin 1, Transient Receptor Potential Channel Interacting; IGF: Insulin like growth factor; VEGF: Vascular endothelial growth factor.

PanCa shows a proclivity for almost about 5 to 7 years of retention rate. Over the years it has been observed that a significant number of patients execute an immensely impoverished prophecy. Recent clinical studies clearly depict that throughout a long period of time; over 10 to 11 years, cellular level observation shows a clear tendency to originate various invasive proficiency. These series of phenomena conciliate the detection factors as well as root out the precursor lesions in PanCa[19]. From recent clinical studies, it is observed that the prior detection of these precancerous lesions put forward the possibility to reduce the death rate. The studies also delineate the fact that several non-intrusive prototype lesions exhibit malignant PanCa. From the surgical history of PanCa, it has been observed that patients having a previous history of PDAC may have microscopic pancreatic intraepithelial neoplasms (PanINs). Furthermore, these multifocal PanINs is clinically allied with diagnosable lobulocentric atrophy. Moreover, Intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCN) are another couple of prominent pre-cancerous lesions which give rise to PanCa. These lesions are often considered to form cysts as well[20]. The surgical treatment and revelation of these MCN, IPMNs and PanINs can often create disturbance in the advancement to incursive PanCa. These eventually shows a high efficacy to save the lives of cancer patients[3,20].


Due to epigenetic alterations, oncogenic signaling pathways specifically derived from transcriptional deregulation create a trademark to PanCa. 5-Hydroxymethylcytosine (5-hmC) is a chemical (epigenetic) modification of DNA at regulatory regions that result in the generation of 5-methylcytosine (5-mC) residue and has been thoroughly studied in PanCa. Genome analysis of 5-hmC occupied loci was done in the cell lines of short-passaged PanCa. As a result, surprising patterns of alteration were seen in neoplastic tissues in primary cancer patients[19,21]. It was observed that near the open chromatin regions, the 5-hmC was very much enhanced and thus tends to show upregulation of the allied transliteration[22]. The transcripts involve a few important oncogenic signaling pathways enmeshed in pancreatic neoplasia, such as KRAS, master regulator of cell cycle (MYC), BRD4 and VEGFA where BRD4 tends to be highly overexpressed in nature. In terms of functional approach, accession of 5-hmC at promoter BRD4 was implicated along with the transcript expression elevation specifically in primary patient samples. It was also noticed that the in in-vivo experiments the growth of PanCa is highly inhibited by the BRD4 blockage. Concisely, it can be said that in human PanCa and oncogenic enhancers, partisan enhancement and 5-hmC reallocation tend to be an important regulatory mechanism[22,23].


In PanCa, some important pathways are Raf/Ras/ERK. MEK interposes specific cellular responses to a few growth factor actions. In the past years, inhibitors emergence is highly noticed that directly target KRAS. This circumvents the long-harboured speculation that drugs cannot be produced by KRAS. In PDAC, several attempts have been made to target this important oncogenic pathway in various approaches. The downstream regulation of frequently mutated KRAS is eventually considered to be an esoteric drug target[24,25]. On the other hand, owing to the offsetting mechanism that involves the enzyme, geranylgeranyl transferase, the upstream regulation of KRAS, using inhibitors like farnesyltransferase has been completely nugatory[26]. It is also observed that the inhibitors like MRTX8, AMG510 and others specifically target only the KRAS mutant variant such as G12C[27,28]. Over 1%–5% of PDACs portray this kind of mutation and the progress is really promising. In PDAC, to regulate the antitumor pursuit in KRAS, the genetic inhibition of some autophagy regulators reciprocally enhances the propensity of ERK inhibitors (Table 1)[29].

Table 1 Targeting various characteristics of pancreatic carcinomas and their associated therapeutic strategies.
Potent therapeutics
Cancer Hallmarks
TGF-β pathway inhibitors HGF; Met pathway inhibitorsActivating invasion/metastasis
JAK/STAT pathway inhibitors; BTK inhibitors; Src inhibitors; COX-2 inhibitorsTumour-promoting inflammation
NRF2 pathway inhibitors; HIF-1 pathway inhibitors; PKCδ-PKD1 inhibitors; Amino acid transporter inhibitors; α-Glucosidase inhibitorsDeregulating cellular metabolism
EGF pathway inhibitors; Ras/Raf/ MEK/ERK pathway inhibitors; PI3K/AKT/mTOR pathway inhibitors; Wnt pathway inhibitors; PDGF pathway inhibitors; SCF/c-Kit pathway inhibitors; ALK pathway inhibitors; Hedgehog pathway inhibitorsSustaining proliferative signalling
IGF pathway inhibitors; NF-κB pathway inhibitorsResisting apoptosis
VEGF pathway inhibitorsInducing angiogenesis
Shh pathway inhibitors; FAK inhibitors; Src inhibitors; EGFR inhibitorsExpansive desmoplasia
Aurora kinase inhibitors; Cyclin-dependent kinase inhibitorsEluding growth suppressors
PD-L1 inhibitors; CTLA-4 inhibitorsAvoiding immune destruction
PARP inhibitors Photodynamic agents; Bromodomain inhibitors; HDAC inhibitorsGenome instability and damage

Epidermal growth factor receptor (EGFR) functions in a significant way in PanCa specifically in terms of tumorigenesis. Epidermal growth factor (EGF) is one of the classic pathways that works in a dysregulated manner in PDAC and is thus often considered as a potent therapeutic target. EGF signaling pathway inhibitors are considered as one of the efficient and significant regulators for cellular viability. These pathway regulators often mediate a wide range of signaling activities, precisely Jak-STAT, Akt/PI3K, Ras/Raf/ and MEK/ERK[29,30]. In PanCa patients, it is often noticed that affirmative activation and regulation of EGFR works effectively for the activation of KRAS and ERK and this persuades the formation of tumor more profoundly[31]. It is found that in Phase III clinical trial, the add-on of erlotinib elevates more positive improvements in cell survival in PanCa patients. The presence of KRAS gene (wild type) in PDAC tumors with a tiny proportion also leads to a significant improvement in PDAC patient survival[27,31].


In case of tissue development and maintenance in both embryos and adults, The Wnt signaling pathway plays a critical role. Digressive activation of this Wnt pathway has been closely associated with cancers like PanCa, specifically to the severely affected digestive tract. It is observed that Cancer stem cells are strongly associated with the activation of this pathway[32]. Furthermore, a precise monoclonal antibody named Wnt inhibitor vantictumab, which eventually targets the decrepitate receptor. This depicts a huge responsive activity of tumors and is often found to be combined with gemcitabine[33].


In several cell lines of PanCa, the occupancy of c-Kit has been clearly mentioned. The stem cell factor tends to reinforce the differentiation as well as the proliferation of cells and also seems to be expressing towards its ligands. Masitinib tends to strongly inhibit both the platelet derived growth factor and stem cell factor signaling pathways, thus delivering such extremely promising outcomes. This affirmative feedback is often found to be combined with gemcitabine[34]. Moreover, this c-Kit pathway inhibitors effluxes the overexpressed ACOX1 marker which elucidates the efficiency in cancer patients[35].


The inhibitors of some specific signaling pathways like PI3K/mTOR and Akt bring into play some indispensable control over multifarious processes that are closely related to the growth and survival of cells in case of disease as well as health[36]. The mTOR/Akt and PI3 pathways also play distinctive key roles in several important cellular mechanisms like cell invasion, adhesion, and migration[37].


Whole genome and exome sequencing has shown that a considerable portion of PDAC patients also carries non-germline mutations in chromatin remodelling complexes and epigenetic regulators, such as ARID1A/B, MLL2/3/4, PBRM1, SMARCA2/4, and KDM6A in addition to germline mutations. Moreover, the inactivation of KDM6A, MLL3, and MLL5 (histone modification enzymes) and non-germline mutations in ARID1A occurred simultaneously with oncogenic KRAS in insertional mutagenesis screening of sleeping beauty transposon[38]. Vincent et al[39] discovered that the histone-modifying enzyme-coding genes were mutated in all of the malignancies in our screen. These mutations helped oncogenic KRAS accelerate the progression of PDAC, indicating that changes to the epigenome are crucial for accelerating PDAC. These results demonstrate the importance of epigenetic regulation in the progression of PanCa[40].

Transcriptional silencing is linked to abberant CpG island methylation of multiple tumor suppressor genes, including p16, in pancreatic and other carcinomas. In 15% of PanCa, the p16 gene is reported to be inactive due to hypermethylation of the CpG island. With higher PanIN grades, there is a greater tendency for the loss of p16 protein production, The ppENK gene exhibits anomalous methylations in pancreatic carcinomas, as was recently established using representational difference analysis and methylation CpG island amplification (MCA)[41].

PENK DNA methylation has been widely observed in precancerous lesions of varying severity, including extra- and intraluminal PTs and CPs, PanINs, IPMNs, and mucinous cystic neoplasms. Changes in PENK methylation increased with increasing coverage of tumor tissue, but were absent in autoimmune pancreatitis (AIP) and adjacent normal pancreatic tissue[3].

The m6A demethylase ALKBH5 was found to be downregulated in a gemcitabine-treated patient-derived xenograft model, and its overexpression made PDAC cells more sensitive to treatment. Reduced ALKBH5 levels predict poor clinical outcome in PDAC and other malignancies. Furthermore, both in vitro and in vivo, downregulation of ALKBH5 greatly promotes PDAC cell proliferation, migration, and invasion, whereas overexpression has the opposite impact. The m6A global profile indicated changes in the expression of certain ALKBH5 target genes, such as Wnt inhibitor 1 (WIF-1), which associated with Wnt signaling pathway mediation and WIF-1 transactivation[42].

Met-enkephalin, a tonically active inhibitory factor that interacts with the opioid growth factor receptor, is encoded by the ppENK gene. Met-enkephalin was found to slow the growth of various human cancers, including PanCa, according to Zagon and colleagues. Comb and associates claim that the CpG island methylation of ppENK directly prevented a positively active transcription factor from binding, which in turn suppressed the production of the gene. Given this, it is a possible outcome that cell growth and carcinogenesis of the pancreas are promoted because of the methylation of the ppEK gene[41]. Moreover, α-catenin, angiogenesis inhibitor BAI3, CTNNA2, DPP6 (dipeptidyl-peptidase), GUCY1A2 (guanylate cyclase), heterotrimeric G-protein-coupled receptor, protein kinases like PRKCG, and Q9H5F0- these genes were often altered at significantly lower frequencies[43]. According to the reports of Li et al[44] a total of 16420 genes having methylation information were found to be differently methylated, including 40 and 831 significantly hypomethylated and hypermethylated genes, respectively. SARM1, IRX4, IRF4, FOXC2, EN2, ZSCAN23, PTPN5, HOXB4, CACNA1, and IGF2BP1 were the 10 genes with the most significantly different methylation patterns. The 10 genes with the most different methylation patterns were REG4, C11orf34, BRD9, S100A16, HIST1H2BK, STATH, LRRC31, UBD, MIR548A1, and PSMG3[45].

Processes like the differentiation of neurons in the CNS, neuropeptide signaling pathway and organ development at the embryonic stage, were the most observed enrichment functions. According to the study, these genes were primarily engaged in signaling pathways for neuroactive ligand-receptor interaction, cAMP, salivary secretions, glutamatergic synapses, calcium, morphine addiction, circadian rhythm, nicotine addiction, and pancreatic secretions. Genes that significantly affect survival were included as taxonomic features in order to define molecular subtypes of PDAC in relation to prognosis[46]. An important finding from the univariate Cox proportional hazards regression model developed for clinical factors indicated that age should be considered as a significant parameter related to patient survival. These 135 significantly differentially methylation genes were included in the above-mentioned multivariate regression model together with age as a covariate to find variables that independently influence prognosis. Using multivariate Cox regression models, 78 differentially methylation genes substantially linked with prognosis were discovered[46,47].

Chatterjee et al[5], identified "regulation of ion transport", "alpha/beta interferon signaling", "morphogenesis and development" and "transcriptional dysregulation" as the four most statistically significant extended terms. Voltage-gated ion channels are membrane proteins that selectively transport ions and are activated by changes in membrane potential. The activation of channels permits potassium ions to move along the electrochemical gradient. Hypermethylation of the KCNA3 gene promoter may explain the poor expression of Kv1.3 in PDAC. The modulation of ion channels has been demonstrated to play a significant role in the regulation of cell death, evasion, and survival in the context of PDAC invasion and development.

In a study by Nones et al[48] 25 pathways were reported to be significantly affected by DNA methylation in PDACs. Axon guidance was one of the most significant (adjusted P value 5 1.91E-05) and was supported by MetaCore pathway analysis. This pathway was recently implicated in PDAC. Other pathways identified here as enriched for genes aberrantly methylated including cell adhesion, hedgehog signaling, TGF-b, integrin signaling and WNT/NOTCH signaling are well-known key cancer signaling previously described to be genetically altered in PDAC. WNT signaling has been reported to be aberrant methylated in PDAC cell lines. Our results confirm that this pathway is aberrantly methylated in this large cohort of PDAC. Stellate cell activation (adjusted P value3.26E-05) another interesting pathway identified here as significantly affected by DNA methylation deserves further investigation due its importance in PDAC. Pancreatic stellate cells are the main fibroblastic cells in PDAC and are known to interact with PanCa cells creating the fibrotic microenvironment of PDAC. It is hypothesized that the fibrous microenvironment of PDAC creates a barrier that impairs the delivery of chemotherapeutic drugs and promotes aggressive behaviour of tumor cells. Known genes are involved in astrocyte activation [cyclooxygenase-2, transforming growth factor-beta receptor 1, EGFR, tumor necrosis factor-alpha and MET were hypomethylated in PDAC and confirmed by bisulfite amplicon deep sequencing[48].

miRNAs are frequently suppressed in cancer cells and have the potential to act as tumor suppressors. Several miRNAs have been implicated in the development and spread of cancer in the pancreas, and it may one day be possible to stop the disease's progression by increasing the activity of a particular miRNA within a cell. The Food and Drug Administration (FDA) -approved drug Miravirsen, which employs miRNA to treat hepatitis C, has sparked interest in miRNA-based medicines for the treatment of PanCa. Regrettably, no treatments employing miRNAs or siRNAs that are comparable to them have been tried in clinical trials to treat PanCa, therefore miRNA will not be explored in great detail in this review. Nevertheless, we recommend individual study into the state of the art in miRNA studies[49].

In addition to confirming the mutations in the tumor suppressor and classical PDAC-associated oncogenes listed above, sequencing efforts have also revealed mutations in a variety of chromatin-modifying enzymes and complexes. The chromatin remodelers like, SWI/SNF family which alters nucleosome structure using ATP and accessibility of DNA in order to control gene transcription, includes the ARID1A component as one of their most often altered genes. 6% of the ARID1A mutations in human PDAC were found using multiplatform sequencing analysis. Although the role of ARID1A as a PDAC-associated tumor suppressor gene is well documented, lymph node or distant metastases do not coincide with its expression levels. Instead, they are related to tumor stage and differentiation. When ARID1A is knocked out, acinar to ductal metaplasia and PanIN lesions develop as a result[41]. It's interesting to note that a recent study using genetically altered PanCa mice models demonstrated the importance of the survival gene Arid1a, whose absence inhibits cell development and causes cell death. In Ras-driven animal models, the deletion of ARID1A also prevents cell growth, leading to the emergence of inactive and low-quality cystic precursor lesions known as IPMNs[50]. The progression of Arid1a-deficient progenitor cells to adenocarcinomas, however, occurs during carcinogenesis via routes involving Tp53 loss or Myc overexpression. PDAC has also been linked to mutations in the SWI/SNF subunits SMARCB1, ARID1B, BRG1, PBRM1, SMARCA2, and SMARCA4. In PanCa cell lines, BRG1 inactivating mutations and deletions have been discovered. BRG1, a crucial entity of the SWI/SNF chromatin remodelling complex, is an ATP-dependent helicase. Neoplastic lesions that mirror human intraductal papillary mucinous neoplasms are produced as a result of BRG1 deletion and KRAS mutation, which aids in the progression of PDAC[41,51].

Methylation at particular genomic locations may put patients at risk for tumor recurrence following total surgical removal and may be a sign of local and/or systemic metastasis. The surgical resection margin methylation profile may be used as a biologic marker in the absence of histologic disease to detect remaining pancreatic tissue that is susceptible to tumor recurrence or that harbours multi-focal disease throughout the gland. The link between methylation abnormalities and Auto immuno pancreatitis (AIP), a representative Immunoglobulin G4 (IgG4)-related illness, has yet to be determined. Through methylation array research using the Methylation 450K BeadChip array, the scientists discovered that sphingosine kinase inhibitor (SKI) may have a major methylation anomaly in AIP and explored the connection of SKI with AIP clinicopathological characteristics. AIP had a considerably lower SKI methylation ratio than PDAC and nurse practitioner (NP). Furthermore, the immunohistochemical staining-index (SI) score for SKI in AIP was substantially greater than in NP, despite no significant difference between AIP and PDAC[52]. Both the serum IgG4 concentration and the SKI methylation ratio showed a strong negative connection between the SI score and the methylation ratio. SI and the serum IgG4 concentration were shown to be somewhat positively correlated. Givien that SKI is regarded as an oncogene, hypomethylation of SKI and carcinogenesis may be connected to AIP[53]. Additionally, the association between serum IgG4 levels and SKI methylation raises the possibility that SKI plays the role in the aetiology of AIP. NPTX2, along with Cyclin D2, FOXE1, TFPI2, ppENK, and p16 all had hypermethylation events (10%) according to a research by Kinugawa et al[54]. However, compared to NCA and NP, AIP had a considerably greaterTFPI2 methylation ratio.


PDAC is a deadly illness with few therapy options. According to new research, PDAC includes numerous layers of epigenetic alterations. Because the change is possibly reversible, it is a possible therapeutic target. Epigenetic changes can potentially affect the tumor microenvironment, modulating and enhancing treatment. Because epigenetic changes occur early in the disease, epigenetic markers can also be employed as diagnostic screening tools. Immunotherapy is being used more frequently to treat solid organ tumors, however there is no benefit for PDAC because most patients do not respond to these new treatments[55,56]. Because epigenetic processes regulate underlying immune cell activities, resulting in an anti-tumor response, combining immunotherapy and epigenetic therapy may improve patient outcomes even more. PDACs are currently classified as three to five subtypes according on the system used[57,58]. Using transcriptomic profiling, two primary molecular subtypes of PDAC were discovered: classical and basal[59]. The traditional kind has a better prognosis and clinical significance. Basal subtypes have altered the methylation of effectors and inhibitors of the Wnt signaling pathway by analyzing the epigenomic landscape. Classical tumors are hypomethylated, resulting in upregulation of the cholesterol transporter NCP1L1[60]. Furthermore, basal tumors were discovered to contain dysregulation of multiple genes related with established oncogenic signaling networks, including the MYC, erythroblastic oncogene B/EGFR, and transforming growth factor (TGF) signaling pathways. Chronic pancreatitis is a well-known risk factor for PDAC, which is consistent with the previously documented general link between tumor and inflammation[61,62]. Early stage PanCa caused by inflammation is linked to epigenetic alterations. Damage to the pancreatic epithelium during a pancreatitis episode results in long-lasting transcriptional and epigenetic remodelling that creates epithelial memory that protects against strokes in the future[63].

Reader proteins, have lately been identified as prospective therapeutic targets, in particular the chromatin adaptors of the bromo and extra C-terminal (BET) family, after directly engaging with the histone tails with acetylated lysine residues, these proteins with bromodomains can bind transcription factors to the DNA, boosting the acetylation-induced transcriptional activation. BET proteins use the epigenetic landscape in this way to support the growth of PDAC cells. Given the wide variety of abnormal epigenetic marks that are possible targets for the advancement of anticancer therapy, the study of and application of epigenetic enzyme inhibitors for the anti-cancer therapy show promise[49,64].

Cell interactions and released substances can cause epigenetic alternations. It has been demonstrated that PDAC cells induced DNA methylation of the SOCS1 gene, acytokine supressor and cancer promoting growth factor, to boost tumor cell proliferation in vitro[63,65]. Clinical evidences demonstrating a higher 3-mo overall survival in patients missing SOCS1 methylationl end credence to this. In PDAC, lysine demethylase 3A (KDM3A) is an effective epigenetic regulator of immunotherapy responses. This enzyme controls the EGFR expressions[66]. Tumors produced by cancer cells deficient in KDM3A have infiltrating immune cells that are responsive to immunotherapy. To distinguish between PDAC and cancer precursor phase, methylation -specific electrophoresis was used to determine the methylation status of the MUC1, MUC2, and MUC4 genes in pancreatic fluids[67]. Additionally, the methylation status of the mucin genes was examined using machine learning, and it was discovered that MUC1 and MUC4 hypomethylation levels were significantly correlated with poor prognosis[68].

Through the suppression of Hedgehog (Hh) signaling, improved gemcitabine delivery was shown in preclinical investigations. Clinical studies were conducted for a number of cancers, but they were unsuccessful and did not progress to phase III trials[69]. However, preclinical research using epigenetic targeting of the proteins known as BET bromodomains, which controls the transcriptional output of Hh signaling, demonstrated positive results in vitro, suggesting possible synergistic therapeutic approaches[70]. BET bromodomain proteins are thought to be crucial contribution to PDAC development and are a topic of active investigations[71]. Based on the transcription factor GATA-binding factor 6 (GATA6)'s function as a regulator of the traditional PDAC subtype identity, the method to induce subtype switching in PDAC has been further investigated. A basal state is provided in PDAC by GATA6 depletion[72]. As a regulator of GATA6 transcription in PDAC, the histone methyltransferase zeste homologue 2 (EZH2) enhancer prevents the decreased EZH2-GATA6 and induced gene signatures present in traditional PDAC subtypes. Therefore, a potential target for PDAC treatment in the future is the EZH2-GATA6 axis[73]. Tazemetostat, an EZH2 inhibitor, has been FDA-approved for use in the treatment of advanced epithelioid sarcoma and is currently being investigated in a phase II research in conjunction with ICI in the treatment of other solid tumors, including PDAC (NCT04705818)[74]. A hostile squamous cell subtype is promoted to differentiate in PDAC by epigenetic silencing of GATA6. Using genome-wide epigenetic mapping of the alterations 5-methylcytosine and 5-hydroxymethylcytosine (5hmC), this epigenetic dysregulation was demonstrated[75]. Due to decreased production of the enzyme 5-methylcytosine hydroxylase TET2, these transcriptional subtypes exhibit a higher loss of 5hmC. In addition, reduction of SMAD4 expression revealed decreased 5hmC and GATA6, resulting in a more squamous-like tumor. Blocking DNA methylation by utilizing the DNA methyltransferase (DNMT) inhibitor 5-azacytidine slows the growth of typical PDAC tumor. In contrast, utilising the same medication or DNMT knockdown via small interfering RNA boosted hyaluronic acid synthesis, ultimately increasing the advancement of PDACI[76]. Epithelial cells from normal pancreata and PDAC underwent transcriptomic and DNA methylomic analysis, which identified a subpopulation characterised by hypomethylation of repetitive regions, which in turn triggers an interferon-linked transcriptional programme[77]. The relationship between cell-of-origin and epigenetics and tumor heterogeneity can be seen in the fact that tumors with low methylation were more aggressive than tumors with high methylation, which kept more of their cell-of-origin characteristics[78].

A clinical trial examining the medication in solid tumor types, including PDAC, and the recent FDA approval of the EZH2 inhibitor tazemetostat for the treatment of advanced epithelioid sarcoma show a potential clinical relevance of the found EZH2-GATA6 axis in PDAC tumor[79]. Numerous researches have examined how DNA methylation mechanisms control the expression of genes in various TME components[80]. For instance, 5-azacytidine, a DNA methyltransferase (DNMT) inhibitor, inhibited global DNA methylation in epithelial PDAC cells and cancer-associated fibroblasts (CAFs), which slowed the evolution of PDAC[75]. In immunocompetent PDAC models, DNMT inhibition increased CD4 and CD8 T-cell infiltration and significantly reduced tumor size. Espinet et al[77] have discovered a link between low DNA methylation levels and subpar PDAC patient outcomes. They show that tumors with low levels of overall DNA methylation in the epithelial cells exhibit increased expression of endogenous retroviral transcripts, robust double-stranded RNA sensing machinery engagement, activation of an interferon signature, and stromal cell reprogramming that is pro-tumourigenic in the PDAC TME. Clinical trials for a sequential strategy based on HDAC/DNMT inhibition, chemotherapy, and then PD-L1 blocking are now being conducted in PDAC, and the findings are highly anticipated[81].

Specifically, nucleoside-like inhibitors induce cytotoxicity through DNA damage brought on by the creation of DNMT-DNA abducts, disrupt DNA methylation, and encourage the re-expression of dormant genes. Both outcomes support anticancer action[82]. Additionally, RNA modification of N6-methyladenosine (m6A) is a unique strategy for dynamic and reversible epigenetic control that has been discovered by researchers. By triggering the Wnt signaling cascade and changing Wnt I[82].

Inhibitory factor 1 (WIF-1), m6A accelerates the course of PanCa. Demethylase, m6A rubber, and the alkylation repair protein 5 (ALKBH5) homolog are increased in gemcitabine-treated sensitized PDAC cells. By demethylating m6A and consequently reducing WIF-1 and deactivating Wnt signaling, it slows the growth of tumors. In vitro and in vivo development and invasiveness are accelerated when PanCa cells lack ALKBH5[42,83]. As a result, ALKBH5 might be a brand-new target for PanCa treatment. Numerous studies have shown how DNMT inhibitors affect PanCa cell lines in vitro by inhibiting them, radiosensitizing them, and immunological sensitizing them. PanCa DNA repair regulation is mediated by H3K36 methylation. H3K36 is a SETD2-dependent protein that is essential for HR repair. Demethylating H3K36 by demethylase KDM4A alters heart rate. A transcription factor for MHCII, RFXAP has been linked to the inhibition of tumor growth. PDAC survival was favourably linked with RFXAP deficiency[84]. Ding et al[85] found that the natural flavonoid fisetin regulates H3K36 methylation to promote RFXAP and KDM4A expression and interferes with HR, leading to DNA damage and PDAC S-phase arrest[85]. Therefore, this tactic may constitute a cutting-edge therapeutic method for treating PanCa. DNMT inhibitors (DNMTis) are undertaking Phase I/II clinical trials in patients with PanCa and have been shown to sensitize PDAC cells to immune checkpoint blockade treatment and chemotherapy[86]. Decitabine, alongside 5-aza, and guadecitabine are DNMTs used for PDAC. Haematological malignancies are also accepted to be treated with HDAC inhibitors (HDACis)[87]. Another therapeutic epigenetic approach for PanCa patients is HDAC inhibition. In PanCa cells, HDAC is, which includes SAHA and CUDC-101, can downregulate apoptotic inhibitory proteins including survivin and XIAP. Additionally, these HDACs can make PanCa more radiosensitive and make it cytotoxic[88]. AR-42, which is another potent HDACi against PanCa cells, can inhibit cell proliferation via inducing cell cycle arrest at G2 phase. Additionally, it can induce DNA damage, apoptosis, and p53 expression, suggesting that it may have therapeutic promise for the treatment of PanCa[89]. In addition to that, reader proteins with different bromodomains that attract proteins implicated in tumor initiation and elongation are blocked by the BET inhibitor JQ1 from binding to the BET domain. In the framework of personalized medicine, Bian et al[90] defined a novel technique for PDAC classification and management based on sensitivity to JQ1 treatment. In order to select PanCa patients with unregulated c-MYC signaling pathways and demonstrate that these selected tumors exhibited greater susceptibility to BET inhibitor JQ1 treatment, the technique involved molecularly characterizing patient xenografts. According to the study, administering BET inhibitors in conjunction with conventional anticancer regimens may constitute an efficient therapy option for individuals who have been carefully chosen and categorized (Table 2)[83,91].

Table 2 Current ongoing trails targeting epigenetic therapy (combination drugs) in Pancreatic Cancer.
Drug names
Combination agents
Trail phase
NCT number
Panobinostat vorinostatVarious antineoplastic drugsPhase 1NCT03878524
VorinostatCapecitabine + radiationPhase 1/2NCT00948688
TazemetostatDurvalumab/gemcitabinePhase 2 recruitingNCT04705818
DurvalumabTazemetostatPhase 2NCT04705818
Romidepsin, azacitidineDurvalumab, lenalidomide, nab-paclitaxelPhase 1/2 recruitingNCT04257448
AzacitidineChemotherapy after progressionPhase 2 activeNCT01845805
VorinostatGemcitabine, sorafenib +/−, radiationPhase 1 activeNCT02349867
CC-486 (oral azacitidine)Phase 2 activeNCT01845805
Azacitidine, not recruitingPembrolizumabPhase 2 activeNCT03264404
TazemetostatDurvalumabPhase 2NCT04705818
MK-8628-Phase 1 completedNCT02259114
EntinostatNivolumabPhase 2 completedNCT03250273
DecitabineTetrahydrouridinePhase 1 completedNCT02847000
VorinostatCapecitabinePhase 1 completedNCT00983268
Azacitidinenab-Paclitaxel, carboplatinPhase 1 completedNCT01478685
VorinostatNPI-0052 (marizomib)Phase 1 completedNCT00667082
AzacitidinePembrolizumabPhase 2 recruitingNCT03264404
AzacitidineAbraxane, gemcitabinePhase 2 activeNCT01845805
EntinostatNivolumabPhase 2 activeNCT03250273

Mechanisms of faulty negative control of cell proliferation, in particular immune evasion, can also produce abnormal proliferation in the development of gastrointestinal malignancies, in addition to unchecked proliferation brought on by cell cycle dysregulation[92]. For instance, it was discovered by researchers that during PanCa, H3K4me3 of the BCL2L1, CFLAR, and MCL-1 gene promoters upregulates the production of the anti-apoptotic proteins Bcl-x, FLIP, and MCL-1, as well as the BAK1, BAX, and BCL2L11 gene promoters of Bak and Bax. Proapoptotic proteins like the Bim protein, for example, have their expression downregulated[93]. These six apoptosis-controlling genes are all essential for PanCa growth and development[94].

Initial investigations with human pancreatic cell lines showed that silencing KMT2D lowered the number and proportion of cells in G0/G1, which was accompanied by a drop in H3K4me1/2/3, indicating that histone methylation is actually involved in cells cycle management[95]. Further research has primarily focused on CKI control. P15 and P21 genes, which encode two often reported CKIs, show higher levels of H3K27me3 and H3K9me3 and lower levels of H3K4me2/3 in gastrointestinal malignancies such as GC, CRC, HCC, and PanCa[96]. Upstream lncRNAs such as BLACAT1, SNHG17, and CASC15 can decrease P15 and P21 expression and cause G0/G1 checkpoint deficit. DZNep (3-deazaneplanocin A), a powerful pharmacologic inhibitor of S-adenosylhomocysteine hydrolase, modifies chromatin accessibility via inhibiting histone methyltransferases such as EZH2[97,98]. It results in a large decrease in H3K27me3 (a primary repressive histone mark) levels, as well as a significant decrease in cell proliferation and migration in CRC. Similar effects can be seen in PanCa, with decreased global H3K27me3 levels leading to re-expression of miR-218, limiting cell growth, encouraging apoptosis, and finally triggering cell cycle arrest in PanCa cells[99]. Another study found that DZNep significantly modulates miR-663a and miR-4787-5p expression and consecutively suppresses TGFb1-induced EMT signaling in PanCa[98,100]. UNC1999, an EZH2-specific inhibitor, not only lowers the abnormal H3K27 methylation that characterizes PanCa cells, but it also slows cancer cell proliferation in three model systems[101]. Furthermore, chaetospirolactone has been shown to suppress the activity of the epigenetic regulator EZH2 and consistently decrease H3K27me3 to allow for the transcription of DR4, which then binds to TRAIL and culminates in the activation of initiator caspase-8 and the formation of the death-inducing signaling complex[102]. As a result, diosgenin, garcinol, FBW7 and curcumin analogue CDF have also been identified as potential agents targeting EZH2 to prevent the development of PanCa[97,103]. Amalgamation treatment with the HMT inhibitor panH3K9me chaetocin and an aurorakinase A (AURKA) inhibitor reduces H3K9 methylation at the centrosome, generating mitotic abnormalities that eventually drive aberrant mitotic checkpoint responses and eventually mitotic catastrophe in PanCa[104].


Since PanCa patients have a dismal prognosis, understanding the molecular events that drive this terrible tumor disease is critical for developing alternative and more effective treatment regimens and determining trustworthy diagnostic indicators. The role of epigenetics in the initiation, development, and evolution of PDAC has been demonstrated by advances in high throughput sequencing and genome-wide association studies. This review covers the major epigenetic signaling pathways as well as how the epigenetic machinery is altered or 'hijacked' in PanCa. Recent epigenetic research has considerably expanded our understanding of the regulatory characteristics involved in PanCa initiation, and progression, along with metastasis tumor. As discussed in this article, DNA-based epigenetic processes have been shown to play a role in PanCa and may serve as potential therapeutic targets aimed at rectifying epigenetic dysregulation of cellular machinery. Initial clinical trials with DNMT inhibitors at stages I-III are presently underway, paving the path for the creation of innovative, and hopefully more successful, 'epidrugs' for patients with PanCa. As a result, we believe that targeting epigenetic regulators and modulators with successful pharmaceutical or even immunotherapeutic techniques would be a game changer in the fight against this aggressive cancer. One significant restriction of using such epigenetic reprogramming of PDAC tumors is the danger of pleiotropic effects, which occur when certain components of the epigenetic machinery have opposite effects in different cellular compartments. Recent improvements in single-cell sequencing technologies that provide multi-omics information from the genome and transcriptome may be useful in determining the specific involvement of the several players in the epigenetic regulation of PDAC tumors. Overall, manipulating the epigenetic machinery, either alone or as part of a combination treatment plan, has the potential to reprogram the aggressive PDAC tumor profile to a less aggressive or easily identifiable and curable state, thereby benefiting patients in the future. In conclusion, we conclude that when cancer-associated signaling pathways are evaluated as a combined shift in "genomic-epigenomic-and-nuclear" structure, an even more realistic picture of PanCa will be obtained. Early preneoplastic lesions in this organ appear to require only a few mutations to initiate a process of aberrant organogenesis via self-reinforcing pathological loops. During metastatic progression, epigenomic landscapes defined by the differential acquisition of enhancers and super-enhancers appear to be required to maintain inheritable, cancer-associated gene expression patterns that support the heterogeneous differentiation of human PanCa tumors. This has given unique insights into an arsenal of novel, potentially actionable signaling pathways that were not previously achieved through genomic analyses, supporting the notion that effective future PDAC therapeutic regimens will require precision medicine approaches that include epigenomic targets.


First, we would like to thank all the authors and clinicians whose valuable work has supported us in writing this review. Second, we also acknowledge clinicians from Tata Medical Center namely Dr. Paromita Roy along with clinicians from Apollo Multispecialty Hospital namely Dr. Sumit Gulati and Dr. Supriyo Ghatak. We would also like to thank Prof. Bitan Kumar Chattopadhay from Department of General Surgery, IPGMER & SSKM Hospital, Kolkata and Prof. Shibajyoti Ghosh from Department of General Surgery, Medical College and Hospital, Kolkata, India. Dr. Aniruddha Chatterjee would like to thank Rutherford Discovery Fellowship from the Royal Society of New Zealand, Department of Pathology, Dunedin School of Medicine, University of Otago for their support. The authors specifically thank and acknowledge Mr. Saraswan Sikdar.


Provenance and peer review: Invited article; Externally peer reviewed.

Peer-review model: Single blind

Specialty type: Gastroenterology and hepatology

Country/Territory of origin: India

Peer-review report’s scientific quality classification

Grade A (Excellent): A

Grade B (Very good): 0

Grade C (Good): C

Grade D (Fair): 0

Grade E (Poor): 0

P-Reviewer: Niu ZS, China; Jin S, China S-Editor: Liu JH L-Editor: A P-Editor: Xu ZH

1.  Ying L, Sharma A, Chhoda A, Ruzgar N, Hasan N, Kwak R, Wolfgang CL, Wang TH, Kunstman JW, Salem RR, Wood LD, Iacobuzio-Donahue C, Schneider EB, Farrell JJ, Ahuja N. Methylation-based Cell-free DNA Signature for Early Detection of Pancreatic Cancer. Pancreas. 2021;50:1267-1273.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 11]  [Cited by in F6Publishing: 4]  [Article Influence: 2.0]  [Reference Citation Analysis (0)]
2.  Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71:209-249.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 27258]  [Cited by in F6Publishing: 19062]  [Article Influence: 9531.0]  [Reference Citation Analysis (9)]
3.  Bararia A, Chakraborty P, Roy P, Chattopadhay BK, Das A, Chatterjee A, Sikdar N. Emerging role of non-invasive and liquid biopsy biomarkers in pancreatic cancer. World J Gastroenterol. 2023;29:2241-2260.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in CrossRef: 1]  [Cited by in F6Publishing: 1]  [Article Influence: 1.0]  [Reference Citation Analysis (0)]
4.  Thompson ED, Roberts NJ, Wood LD, Eshleman JR, Goggins MG, Kern SE, Klein AP, Hruban RH. The genetics of ductal adenocarcinoma of the pancreas in the year 2020: dramatic progress, but far to go. Mod Pathol. 2020;33:2544-2563.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 17]  [Cited by in F6Publishing: 16]  [Article Influence: 5.3]  [Reference Citation Analysis (0)]
5.  Chatterjee A, Bararia A, Ganguly D, Mondal PK, Roy P, Banerjee S, Ghosh S, Gulati S, Ghatak S, Chattopadhay BK, Basu P, Chatterjee A, Sikdar N. DNA methylome in pancreatic cancer identified novel promoter hyper-methylation in NPY and FAIM2 genes associated with poor prognosis in Indian patient cohort. Cancer Cell Int. 2022;22:334.  [PubMed]  [DOI]  [Cited in This Article: ]  [Reference Citation Analysis (0)]
6.  Hu JX, Zhao CF, Chen WB, Liu QC, Li QW, Lin YY, Gao F. Pancreatic cancer: A review of epidemiology, trend, and risk factors. World J Gastroenterol. 2021;27:4298-4321.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in CrossRef: 111]  [Cited by in F6Publishing: 86]  [Article Influence: 43.0]  [Reference Citation Analysis (9)]
7.  O'Neill RS, Stoita A. Biomarkers in the diagnosis of pancreatic cancer: Are we closer to finding the golden ticket? World J Gastroenterol. 2021;27:4045-4087.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in CrossRef: 14]  [Cited by in F6Publishing: 12]  [Article Influence: 6.0]  [Reference Citation Analysis (1)]
8.  Khalaf N, El-Serag HB, Abrams HR, Thrift AP. Burden of Pancreatic Cancer: From Epidemiology to Practice. Clin Gastroenterol Hepatol. 2021;19:876-884.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 90]  [Cited by in F6Publishing: 91]  [Article Influence: 45.5]  [Reference Citation Analysis (0)]
9.  Schnelldorfer T, Ware AL, Sarr MG, Smyrk TC, Zhang L, Qin R, Gullerud RE, Donohue JH, Nagorney DM, Farnell MB. Long-term survival after pancreatoduodenectomy for pancreatic adenocarcinoma: is cure possible? Ann Surg. 2008;247:456-462.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 339]  [Cited by in F6Publishing: 364]  [Article Influence: 24.3]  [Reference Citation Analysis (0)]
10.  Zhao Y, Yang M, Wang S, Abbas SJ, Zhang J, Li Y, Shao R, Liu Y. An Overview of Epigenetic Methylation in Pancreatic Cancer Progression. Front Oncol. 2022;12:854773.  [PubMed]  [DOI]  [Cited in This Article: ]  [Reference Citation Analysis (0)]
11.  Pandey S, Gupta VK, Lavania SP. Role of epigenetics in pancreatic ductal adenocarcinoma. Epigenomics. 2023;15:89-110.  [PubMed]  [DOI]  [Cited in This Article: ]  [Reference Citation Analysis (0)]
12.  Zhang Z, Zhu R, Sun W, Wang J, Liu J. Analysis of Methylation-driven Genes in Pancreatic Ductal Adenocarcinoma for Predicting Prognosis. J Cancer. 2021;12:6507-6518.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 2]  [Cited by in F6Publishing: 2]  [Article Influence: 1.0]  [Reference Citation Analysis (0)]
13.  Visani M, Acquaviva G, De Leo A, Sanza V, Merlo L, Maloberti T, Brandes AA, Franceschi E, Di Battista M, Masetti M, Jovine E, Fiorino S, Pession A, Tallini G, de Biase D. Molecular alterations in pancreatic tumors. World J Gastroenterol. 2021;27:2710-2726.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in CrossRef: 11]  [Cited by in F6Publishing: 11]  [Article Influence: 5.5]  [Reference Citation Analysis (1)]
14.  Brancaccio M, Natale F, Falco G, Angrisano T. Cell-Free DNA Methylation: The New Frontiers of Pancreatic Cancer Biomarkers' Discovery. Genes (Basel). 2019;11.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 23]  [Cited by in F6Publishing: 24]  [Article Influence: 6.0]  [Reference Citation Analysis (0)]
15.  Thompson MJ, Rubbi L, Dawson DW, Donahue TR, Pellegrini M. Pancreatic cancer patient survival correlates with DNA methylation of pancreas development genes. PLoS One. 2015;10:e0128814.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 43]  [Cited by in F6Publishing: 45]  [Article Influence: 5.6]  [Reference Citation Analysis (0)]
16.  Thompson JK, Bednar F. Clinical Utility of Epigenetic Changes in Pancreatic Adenocarcinoma. Epigenomes. 2021;5.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 3]  [Cited by in F6Publishing: 1]  [Article Influence: 0.5]  [Reference Citation Analysis (0)]
17.  Bararia A, Dey S, Gulati S, Ghatak S, Ghosh S, Banerjee S, Sikdar N. Differential methylation landscape of pancreatic ductal adenocarcinoma and its precancerous lesions. Hepatobiliary Pancreat Dis Int. 2020;19:205-217.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 10]  [Cited by in F6Publishing: 10]  [Article Influence: 3.3]  [Reference Citation Analysis (0)]
18.  Wang SS, Xu J, Ji KY, Hwang CI. Epigenetic Alterations in Pancreatic Cancer Metastasis. Biomolecules. 2021;11.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 3]  [Cited by in F6Publishing: 5]  [Article Influence: 2.5]  [Reference Citation Analysis (1)]
19.  Neureiter D, Jäger T, Ocker M, Kiesslich T. Epigenetics and pancreatic cancer: pathophysiology and novel treatment aspects. World J Gastroenterol. 2014;20:7830-7848.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in CrossRef: 70]  [Cited by in F6Publishing: 67]  [Article Influence: 7.4]  [Reference Citation Analysis (1)]
20.  Zamboni G, Hirabayashi K, Castelli P, Lennon AM. Precancerous lesions of the pancreas. Best Pract Res Clin Gastroenterol. 2013;27:299-322.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 51]  [Cited by in F6Publishing: 53]  [Article Influence: 5.3]  [Reference Citation Analysis (0)]
21.  Guler GD, Ning Y, Ku CJ, Phillips T, McCarthy E, Ellison CK, Bergamaschi A, Collin F, Lloyd P, Scott A, Antoine M, Wang W, Chau K, Ashworth A, Quake SR, Levy S. Detection of early stage pancreatic cancer using 5-hydroxymethylcytosine signatures in circulating cell free DNA. Nat Commun. 2020;11:5270.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 44]  [Cited by in F6Publishing: 48]  [Article Influence: 16.0]  [Reference Citation Analysis (0)]
22.  Fujikura K, Alruwaii ZI, Haffner MC, Trujillo MA, Roberts NJ, Hong SM, Macgregor-Das A, Goggins MG, Roy S, Meeker AK, Ding D, Wright M, He J, Hruban RH, Wood LD. Downregulation of 5-hydroxymethylcytosine is an early event in pancreatic tumorigenesis. J Pathol. 2021;254:279-288.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 4]  [Cited by in F6Publishing: 4]  [Article Influence: 2.0]  [Reference Citation Analysis (0)]
23.  Lomberk G, Dusetti N, Iovanna J, Urrutia R. Emerging epigenomic landscapes of pancreatic cancer in the era of precision medicine. Nat Commun. 2019;10:3875.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 38]  [Cited by in F6Publishing: 41]  [Article Influence: 10.3]  [Reference Citation Analysis (0)]
24.  Michael JV, Goldfinger LE. Concepts and advances in cancer therapeutic vulnerabilities in RAS membrane targeting. Semin Cancer Biol. 2019;54:121-130.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 10]  [Cited by in F6Publishing: 11]  [Article Influence: 1.8]  [Reference Citation Analysis (0)]
25.  Saha G, Singh R, Mandal A, Das S, Chattopadhyay E, Panja P, Roy P, DeSarkar N, Gulati S, Ghatak S, Ghosh S, Banerjee S, Roy B, Chaudhuri D, Arora N, Biswas NK, Sikdar N. A novel hotspot and rare somatic mutation p.A138V, at TP53 is associated with poor survival of pancreatic ductal and periampullary adenocarcinoma patients. Mol Med. 2020;26:59.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 6]  [Cited by in F6Publishing: 7]  [Article Influence: 2.3]  [Reference Citation Analysis (0)]
26.  Choi M, Bien H, Mofunanya A, Powers S. Challenges in Ras therapeutics in pancreatic cancer. Semin Cancer Biol. 2019;54:101-108.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 16]  [Cited by in F6Publishing: 15]  [Article Influence: 2.5]  [Reference Citation Analysis (0)]
27.  Canon J, Rex K, Saiki AY, Mohr C, Cooke K, Bagal D, Gaida K, Holt T, Knutson CG, Koppada N, Lanman BA, Werner J, Rapaport AS, San Miguel T, Ortiz R, Osgood T, Sun JR, Zhu X, McCarter JD, Volak LP, Houk BE, Fakih MG, O'Neil BH, Price TJ, Falchook GS, Desai J, Kuo J, Govindan R, Hong DS, Ouyang W, Henary H, Arvedson T, Cee VJ, Lipford JR. The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity. Nature. 2019;575:217-223.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 843]  [Cited by in F6Publishing: 891]  [Article Influence: 222.8]  [Reference Citation Analysis (0)]
28.  Seton-Rogers S. KRAS-G12C in the crosshairs. Nat Rev Cancer. 2020;20:3.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 24]  [Cited by in F6Publishing: 24]  [Article Influence: 8.0]  [Reference Citation Analysis (0)]
29.  Bryant KL, Stalnecker CA, Zeitouni D, Klomp JE, Peng S, Tikunov AP, Gunda V, Pierobon M, Waters AM, George SD, Tomar G, Papke B, Hobbs GA, Yan L, Hayes TK, Diehl JN, Goode GD, Chaika NV, Wang Y, Zhang GF, Witkiewicz AK, Knudsen ES, Petricoin EF 3rd, Singh PK, Macdonald JM, Tran NL, Lyssiotis CA, Ying H, Kimmelman AC, Cox AD, Der CJ. Combination of ERK and autophagy inhibition as a treatment approach for pancreatic cancer. Nat Med. 2019;25:628-640.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 322]  [Cited by in F6Publishing: 339]  [Article Influence: 84.8]  [Reference Citation Analysis (0)]
30.  Fitzgerald TL, Lertpiriyapong K, Cocco L, Martelli AM, Libra M, Candido S, Montalto G, Cervello M, Steelman L, Abrams SL, McCubrey JA. Roles of EGFR and KRAS and their downstream signaling pathways in pancreatic cancer and pancreatic cancer stem cells. Adv Biol Regul. 2015;59:65-81.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 97]  [Cited by in F6Publishing: 105]  [Article Influence: 13.1]  [Reference Citation Analysis (0)]
31.  Ardito CM, Grüner BM, Takeuchi KK, Lubeseder-Martellato C, Teichmann N, Mazur PK, Delgiorno KE, Carpenter ES, Halbrook CJ, Hall JC, Pal D, Briel T, Herner A, Trajkovic-Arsic M, Sipos B, Liou GY, Storz P, Murray NR, Threadgill DW, Sibilia M, Washington MK, Wilson CL, Schmid RM, Raines EW, Crawford HC, Siveke JT. EGF receptor is required for KRAS-induced pancreatic tumorigenesis. Cancer Cell. 2012;22:304-317.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 380]  [Cited by in F6Publishing: 387]  [Article Influence: 35.2]  [Reference Citation Analysis (0)]
32.  Zhan T, Rindtorff N, Boutros M. Wnt signaling in cancer. Oncogene. 2017;36:1461-1473.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 1646]  [Cited by in F6Publishing: 1382]  [Article Influence: 230.3]  [Reference Citation Analysis (0)]
33.  Davis SL, Cardin DB, Shahda S, Lenz HJ, Dotan E, O'Neil BH, Kapoun AM, Stagg RJ, Berlin J, Messersmith WA, Cohen SJ. A phase 1b dose escalation study of Wnt pathway inhibitor vantictumab in combination with nab-paclitaxel and gemcitabine in patients with previously untreated metastatic pancreatic cancer. Invest New Drugs. 2020;38:821-830.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 55]  [Cited by in F6Publishing: 29]  [Article Influence: 9.7]  [Reference Citation Analysis (0)]
34.  Deplanque G, Demarchi M, Hebbar M, Flynn P, Melichar B, Atkins J, Nowara E, Moyé L, Piquemal D, Ritter D, Dubreuil P, Mansfield CD, Acin Y, Moussy A, Hermine O, Hammel P. A randomized, placebo-controlled phase III trial of masitinib plus gemcitabine in the treatment of advanced pancreatic cancer. Ann Oncol. 2015;26:1194-1200.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 54]  [Cited by in F6Publishing: 63]  [Article Influence: 7.9]  [Reference Citation Analysis (0)]
35.  Fang YT, Yang WW, Niu YR, Sun YK. Recent advances in targeted therapy for pancreatic adenocarcinoma. World J Gastrointest Oncol. 2023;15:571-595.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in CrossRef: 1]  [Cited by in F6Publishing: 1]  [Article Influence: 1.0]  [Reference Citation Analysis (0)]
36.  Li Q, Li Z, Luo T, Shi H. Targeting the PI3K/AKT/mTOR and RAF/MEK/ERK pathways for cancer therapy. Mol Biomed. 2022;3:47.  [PubMed]  [DOI]  [Cited in This Article: ]  [Reference Citation Analysis (0)]
37.  Karar J, Maity A. PI3K/AKT/mTOR Pathway in Angiogenesis. Front Mol Neurosci. 2011;4:51.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 712]  [Cited by in F6Publishing: 768]  [Article Influence: 64.0]  [Reference Citation Analysis (0)]
38.  Takeda H, Rust AG, Ward JM, Yew CC, Jenkins NA, Copeland NG. Sleeping Beauty transposon mutagenesis identifies genes that cooperate with mutant Smad4 in gastric cancer development. Proc Natl Acad Sci U S A. 2016;113:E2057-E2065.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 31]  [Cited by in F6Publishing: 33]  [Article Influence: 4.7]  [Reference Citation Analysis (0)]
39.  Vincent A, Omura N, Hong SM, Jaffe A, Eshleman J, Goggins M. Genome-wide analysis of promoter methylation associated with gene expression profile in pancreatic adenocarcinoma. Clin Cancer Res. 2011;17:4341-4354.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 125]  [Cited by in F6Publishing: 133]  [Article Influence: 11.1]  [Reference Citation Analysis (0)]
40.  di Magliano MP, Logsdon CD. Roles for KRAS in pancreatic tumor development and progression. Gastroenterology. 2013;144:1220-1229.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 276]  [Cited by in F6Publishing: 288]  [Article Influence: 28.8]  [Reference Citation Analysis (0)]
41.  Fukushima N, Sato N, Ueki T, Rosty C, Walter KM, Wilentz RE, Yeo CJ, Hruban RH, Goggins M. Aberrant methylation of preproenkephalin and p16 genes in pancreatic intraepithelial neoplasia and pancreatic ductal adenocarcinoma. Am J Pathol. 2002;160:1573-1581.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 154]  [Cited by in F6Publishing: 170]  [Article Influence: 8.1]  [Reference Citation Analysis (0)]
42.  Tang B, Yang Y, Kang M, Wang Y, Bi Y, He S, Shimamoto F. m(6)A demethylase ALKBH5 inhibits pancreatic cancer tumorigenesis by decreasing WIF-1 RNA methylation and mediating Wnt signaling. Mol Cancer. 2020;19:3.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 122]  [Cited by in F6Publishing: 132]  [Article Influence: 44.0]  [Reference Citation Analysis (0)]
43.  Jones S, Zhang X, Parsons DW, Lin JC, Leary RJ, Angenendt P, Mankoo P, Carter H, Kamiyama H, Jimeno A, Hong SM, Fu B, Lin MT, Calhoun ES, Kamiyama M, Walter K, Nikolskaya T, Nikolsky Y, Hartigan J, Smith DR, Hidalgo M, Leach SD, Klein AP, Jaffee EM, Goggins M, Maitra A, Iacobuzio-Donahue C, Eshleman JR, Kern SE, Hruban RH, Karchin R, Papadopoulos N, Parmigiani G, Vogelstein B, Velculescu VE, Kinzler KW. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science. 2008;321:1801-1806.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 2858]  [Cited by in F6Publishing: 3058]  [Article Influence: 203.9]  [Reference Citation Analysis (0)]
44.  Li X, Zhang X, Lin X, Cai L, Wang Y, Chang Z. Classification and Prognosis Analysis of Pancreatic Cancer Based on DNA Methylation Profile and Clinical Information. Genes (Basel). 2022;13.  [PubMed]  [DOI]  [Cited in This Article: ]  [Reference Citation Analysis (0)]
45.  Xiao M, Liang X, Yan Z, Chen J, Zhu Y, Xie Y, Li Y, Li X, Gao Q, Feng F, Fu G, Gao Y. A DNA-Methylation-Driven Genes Based Prognostic Signature Reveals Immune Microenvironment in Pancreatic Cancer. Front Immunol. 2022;13:803962.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 3]  [Cited by in F6Publishing: 3]  [Article Influence: 3.0]  [Reference Citation Analysis (0)]
46.  Zou T, Shi D, Wang W, Chen G, Zhang X, Tian Y, Gong P. Identification of a New m6A Regulator-Related Methylation Signature for Predicting the Prognosis and Immune Microenvironment of Patients with Pancreatic Cancer. Mediators Inflamm. 2023;2023:5565054.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 1]  [Reference Citation Analysis (0)]
47.  Zheng X, Du Y, Liu M, Wang C. ITGA3 acts as a purity-independent biomarker of both immunotherapy and chemotherapy resistance in pancreatic cancer: bioinformatics and experimental analysis. Funct Integr Genomics. 2023;23:196.  [PubMed]  [DOI]  [Cited in This Article: ]  [Reference Citation Analysis (0)]
48.  Nones K, Waddell N, Song S, Patch AM, Miller D, Johns A, Wu J, Kassahn KS, Wood D, Bailey P, Fink L, Manning S, Christ AN, Nourse C, Kazakoff S, Taylor D, Leonard C, Chang DK, Jones MD, Thomas M, Watson C, Pinese M, Cowley M, Rooman I, Pajic M; APGI, Butturini G, Malpaga A, Corbo V, Crippa S, Falconi M, Zamboni G, Castelli P, Lawlor RT, Gill AJ, Scarpa A, Pearson JV, Biankin AV, Grimmond SM. Genome-wide DNA methylation patterns in pancreatic ductal adenocarcinoma reveal epigenetic deregulation of SLIT-ROBO, ITGA2 and MET signaling. Int J Cancer. 2014;135:1110-1118.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 147]  [Cited by in F6Publishing: 158]  [Article Influence: 17.6]  [Reference Citation Analysis (0)]
49.  Paradise BD, Barham W, Fernandez-Zapico ME. Targeting Epigenetic Aberrations in Pancreatic Cancer, a New Path to Improve Patient Outcomes? Cancers (Basel). 2018;10.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 19]  [Cited by in F6Publishing: 19]  [Article Influence: 3.8]  [Reference Citation Analysis (0)]
50.  House MG, Guo M, Iacobuzio-Donahue C, Herman JG. Molecular progression of promoter methylation in intraductal papillary mucinous neoplasms (IPMN) of the pancreas. Carcinogenesis. 2003;24:193-198.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 127]  [Cited by in F6Publishing: 134]  [Article Influence: 6.7]  [Reference Citation Analysis (0)]
51.  Grzenda A, Ordog T, Urrutia R. Polycomb and the emerging epigenetics of pancreatic cancer. J Gastrointest Cancer. 2011;42:100-111.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 13]  [Cited by in F6Publishing: 10]  [Article Influence: 0.8]  [Reference Citation Analysis (0)]
52.  Hamano H, Kawa S, Horiuchi A, Unno H, Furuya N, Akamatsu T, Fukushima M, Nikaido T, Nakayama K, Usuda N, Kiyosawa K. High serum IgG4 concentrations in patients with sclerosing pancreatitis. N Engl J Med. 2001;344:732-738.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 2026]  [Cited by in F6Publishing: 2093]  [Article Influence: 95.1]  [Reference Citation Analysis (0)]
53.  Umehara H, Okazaki K, Masaki Y, Kawano M, Yamamoto M, Saeki T, Matsui S, Sumida T, Mimori T, Tanaka Y, Tsubota K, Yoshino T, Kawa S, Suzuki R, Takegami T, Tomosugi N, Kurose N, Ishigaki Y, Azumi A, Kojima M, Nakamura S, Inoue D; Research Program for Intractable Disease by Ministry of Health, Labor and Welfare (MHLW) Japan G4 team. A novel clinical entity, IgG4-related disease (IgG4RD): general concept and details. Mod Rheumatol. 2012;22:1-14.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 105]  [Cited by in F6Publishing: 245]  [Article Influence: 20.4]  [Reference Citation Analysis (0)]
54.  Kinugawa Y, Uehara T, Matsuda K, Kobayashi Y, Nakajima T, Hamano H, Kawa S, Higuchi K, Hosaka N, Shiozawa S, Ishigame H, Nakamura T, Maruyama Y, Nakazawa K, Nakaguro M, Sano K, Ota H. Promoter hypomethylation of SKI in autoimmune pancreatitis. Pathol Res Pract. 2018;214:492-497.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 2]  [Cited by in F6Publishing: 2]  [Article Influence: 0.4]  [Reference Citation Analysis (0)]
55.  Zhang CY, Liu S, Yang M. Clinical diagnosis and management of pancreatic cancer: Markers, molecular mechanisms, and treatment options. World J Gastroenterol. 2022;28:6827-6845.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in CrossRef: 1]  [Reference Citation Analysis (2)]
56.  Jamieson NB, Steele CW.   Immuno-Oncology in Pancreatic Cancer. In: Textbook of Pancreatic Cancer. Cham: Springer International Publishing, 2021: 287–304.  [PubMed]  [DOI]  [Cited in This Article: ]
57.  Bailey P, Chang DK, Nones K, Johns AL, Patch AM, Gingras MC, Miller DK, Christ AN, Bruxner TJ, Quinn MC, Nourse C, Murtaugh LC, Harliwong I, Idrisoglu S, Manning S, Nourbakhsh E, Wani S, Fink L, Holmes O, Chin V, Anderson MJ, Kazakoff S, Leonard C, Newell F, Waddell N, Wood S, Xu Q, Wilson PJ, Cloonan N, Kassahn KS, Taylor D, Quek K, Robertson A, Pantano L, Mincarelli L, Sanchez LN, Evers L, Wu J, Pinese M, Cowley MJ, Jones MD, Colvin EK, Nagrial AM, Humphrey ES, Chantrill LA, Mawson A, Humphris J, Chou A, Pajic M, Scarlett CJ, Pinho AV, Giry-Laterriere M, Rooman I, Samra JS, Kench JG, Lovell JA, Merrett ND, Toon CW, Epari K, Nguyen NQ, Barbour A, Zeps N, Moran-Jones K, Jamieson NB, Graham JS, Duthie F, Oien K, Hair J, Grützmann R, Maitra A, Iacobuzio-Donahue CA, Wolfgang CL, Morgan RA, Lawlor RT, Corbo V, Bassi C, Rusev B, Capelli P, Salvia R, Tortora G, Mukhopadhyay D, Petersen GM; Australian Pancreatic Cancer Genome Initiative, Munzy DM, Fisher WE, Karim SA, Eshleman JR, Hruban RH, Pilarsky C, Morton JP, Sansom OJ, Scarpa A, Musgrove EA, Bailey UM, Hofmann O, Sutherland RL, Wheeler DA, Gill AJ, Gibbs RA, Pearson JV, Waddell N, Biankin AV, Grimmond SM. Genomic analyses identify molecular subtypes of pancreatic cancer. Nature. 2016;531:47-52.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 1978]  [Cited by in F6Publishing: 2075]  [Article Influence: 296.4]  [Reference Citation Analysis (0)]
58.  Moffitt RA, Marayati R, Flate EL, Volmar KE, Loeza SG, Hoadley KA, Rashid NU, Williams LA, Eaton SC, Chung AH, Smyla JK, Anderson JM, Kim HJ, Bentrem DJ, Talamonti MS, Iacobuzio-Donahue CA, Hollingsworth MA, Yeh JJ. Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma. Nat Genet. 2015;47:1168-1178.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 1041]  [Cited by in F6Publishing: 1084]  [Article Influence: 135.5]  [Reference Citation Analysis (0)]
59.  Malinova A, Veghini L, Real FX, Corbo V. Cell Lineage Infidelity in PDAC Progression and Therapy Resistance. Front Cell Dev Biol. 2021;9:795251.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 4]  [Cited by in F6Publishing: 4]  [Article Influence: 2.0]  [Reference Citation Analysis (0)]
60.  Koni M, Pinnarò V, Brizzi MF. The Wnt Signalling Pathway: A Tailored Target in Cancer. Int J Mol Sci. 2020;21.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 52]  [Cited by in F6Publishing: 58]  [Article Influence: 19.3]  [Reference Citation Analysis (0)]
61.  Kirkegård J, Mortensen FV, Cronin-Fenton D. Chronic Pancreatitis and Pancreatic Cancer Risk: A Systematic Review and Meta-analysis. Am J Gastroenterol. 2017;112:1366-1372.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 231]  [Cited by in F6Publishing: 228]  [Article Influence: 38.0]  [Reference Citation Analysis (0)]
62.  Del Poggetto E, Ho IL, Balestrieri C, Yen EY, Zhang S, Citron F, Shah R, Corti D, Diaferia GR, Li CY, Loponte S, Carbone F, Hayakawa Y, Valenti G, Jiang S, Sapio L, Jiang H, Dey P, Gao S, Deem AK, Rose-John S, Yao W, Ying H, Rhim AD, Genovese G, Heffernan TP, Maitra A, Wang TC, Wang L, Draetta GF, Carugo A, Natoli G, Viale A. Epithelial memory of inflammation limits tissue damage while promoting pancreatic tumorigenesis. Science. 2021;373:eabj0486.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 37]  [Cited by in F6Publishing: 37]  [Article Influence: 18.5]  [Reference Citation Analysis (0)]
63.  Garcia-Gomez A, Rodríguez-Ubreva J, Ballestar E. Epigenetic interplay between immune, stromal and cancer cells in the tumor microenvironment. Clin Immunol. 2018;196:64-71.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 41]  [Cited by in F6Publishing: 46]  [Article Influence: 9.2]  [Reference Citation Analysis (0)]
64.  Natale F, Vivo M, Falco G, Angrisano T. Deciphering DNA methylation signatures of pancreatic cancer and pancreatitis. Clin Epigenetics. 2019;11:132.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 26]  [Cited by in F6Publishing: 29]  [Article Influence: 7.3]  [Reference Citation Analysis (0)]
65.  Xiao Q, Zhou D, Rucki AA, Williams J, Zhou J, Mo G, Murphy A, Fujiwara K, Kleponis J, Salman B, Wolfgang CL, Anders RA, Zheng S, Jaffee EM, Zheng L. Cancer-Associated Fibroblasts in Pancreatic Cancer Are Reprogrammed by Tumor-Induced Alterations in Genomic DNA Methylation. Cancer Res. 2016;76:5395-5404.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 69]  [Cited by in F6Publishing: 73]  [Article Influence: 10.4]  [Reference Citation Analysis (0)]
66.  Li J, Yuan S, Norgard RJ, Yan F, Sun YH, Kim IK, Merrell AJ, Sela Y, Jiang Y, Bhanu NV, Garcia BA, Vonderheide RH, Blanco A, Stanger BZ. Epigenetic and Transcriptional Control of the Epidermal Growth Factor Receptor Regulates the Tumor Immune Microenvironment in Pancreatic Cancer. Cancer Discov. 2021;11:736-753.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 28]  [Cited by in F6Publishing: 28]  [Article Influence: 9.3]  [Reference Citation Analysis (0)]
67.  Yokoyama S, Kitamoto S, Higashi M, Goto Y, Hara T, Ikebe D, Yamaguchi T, Arisaka Y, Niihara T, Nishimata H, Tanaka S, Takaori K, Batra SK, Yonezawa S. Diagnosis of pancreatic neoplasms using a novel method of DNA methylation analysis of mucin expression in pancreatic juice. PLoS One. 2014;9:e93760.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 28]  [Cited by in F6Publishing: 25]  [Article Influence: 2.8]  [Reference Citation Analysis (0)]
68.  Yokoyama S, Hamada T, Higashi M, Matsuo K, Maemura K, Kurahara H, Horinouchi M, Hiraki T, Sugimoto T, Akahane T, Yonezawa S, Kornmann M, Batra SK, Hollingsworth MA, Tanimoto A. Predicted Prognosis of Patients with Pancreatic Cancer by Machine Learning. Clin Cancer Res. 2020;26:2411-2421.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 26]  [Cited by in F6Publishing: 29]  [Article Influence: 9.7]  [Reference Citation Analysis (0)]
69.  Olive KP, Jacobetz MA, Davidson CJ, Gopinathan A, McIntyre D, Honess D, Madhu B, Goldgraben MA, Caldwell ME, Allard D, Frese KK, Denicola G, Feig C, Combs C, Winter SP, Ireland-Zecchini H, Reichelt S, Howat WJ, Chang A, Dhara M, Wang L, Rückert F, Grützmann R, Pilarsky C, Izeradjene K, Hingorani SR, Huang P, Davies SE, Plunkett W, Egorin M, Hruban RH, Whitebread N, McGovern K, Adams J, Iacobuzio-Donahue C, Griffiths J, Tuveson DA. Inhibition of Hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer. Science. 2009;324:1457-1461.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 2272]  [Cited by in F6Publishing: 2439]  [Article Influence: 174.2]  [Reference Citation Analysis (0)]
70.  Huang Y, Nahar S, Nakagawa A, Fernandez-Barrena MG, Mertz JA, Bryant BM, Adams CE, Mino-Kenudson M, Von Alt KN, Chang K, Conery AR, Hatton C, Sims RJ 3rd, Fernandez-Zapico ME, Wang X, Lillemoe KD, Fernández-Del Castillo C, Warshaw AL, Thayer SP, Liss AS. Regulation of GLI Underlies a Role for BET Bromodomains in Pancreatic Cancer Growth and the Tumor Microenvironment. Clin Cancer Res. 2016;22:4259-4270.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 31]  [Cited by in F6Publishing: 31]  [Article Influence: 4.4]  [Reference Citation Analysis (0)]
71.  Smith SG, Zhou MM. The Bromodomain: A New Target in Emerging Epigenetic Medicine. ACS Chem Biol. 2016;11:598-608.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 87]  [Cited by in F6Publishing: 89]  [Article Influence: 12.7]  [Reference Citation Analysis (0)]
72.  Lomberk G, Blum Y, Nicolle R, Nair A, Gaonkar KS, Marisa L, Mathison A, Sun Z, Yan H, Elarouci N, Armenoult L, Ayadi M, Ordog T, Lee JH, Oliver G, Klee E, Moutardier V, Gayet O, Bian B, Duconseil P, Gilabert M, Bigonnet M, Garcia S, Turrini O, Delpero JR, Giovannini M, Grandval P, Gasmi M, Secq V, De Reyniès A, Dusetti N, Iovanna J, Urrutia R. Distinct epigenetic landscapes underlie the pathobiology of pancreatic cancer subtypes. Nat Commun. 2018;9:1978.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 136]  [Cited by in F6Publishing: 140]  [Article Influence: 28.0]  [Reference Citation Analysis (0)]
73.  Kloesch B, Ionasz V, Paliwal S, Hruschka N, Martinez de Villarreal J, Öllinger R, Mueller S, Dienes HP, Schindl M, Gruber ES, Stift J, Herndler-Brandstetter D, Lomberk GA, Seidler B, Saur D, Rad R, Urrutia RA, Real FX, Martinelli P. A GATA6-centred gene regulatory network involving HNFs and ΔNp63 controls plasticity and immune escape in pancreatic cancer. Gut. 2022;71:766-777.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 17]  [Cited by in F6Publishing: 18]  [Article Influence: 18.0]  [Reference Citation Analysis (0)]
74.  Eyres M, Lanfredini S, Xu H, Burns A, Blake A, Willenbrock F, Goldin R, Hughes D, Hughes S, Thapa A, Vavoulis D, Hubert A, D'Costa Z, Sabbagh A, Abraham AG, Blancher C, Jones S, Verrill C, Silva M, Soonawalla Z, Maughan T, Schuh A, Mukherjee S, O'Neill E. TET2 Drives 5hmc Marking of GATA6 and Epigenetically Defines Pancreatic Ductal Adenocarcinoma Transcriptional Subtypes. Gastroenterology. 2021;161:653-668.e16.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 19]  [Cited by in F6Publishing: 19]  [Article Influence: 9.5]  [Reference Citation Analysis (0)]
75.  Shakya R, Gonda T, Quante M, Salas M, Kim S, Brooks J, Hirsch S, Davies J, Cullo A, Olive K, Wang TC, Szabolcs M, Tycko B, Ludwig T. Hypomethylating therapy in an aggressive stroma-rich model of pancreatic carcinoma. Cancer Res. 2013;73:885-896.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 56]  [Cited by in F6Publishing: 59]  [Article Influence: 5.4]  [Reference Citation Analysis (0)]
76.  Kohi S, Sato N, Cheng XB, Koga A, Higure A, Hirata K. A novel epigenetic mechanism regulating hyaluronan production in pancreatic cancer cells. Clin Exp Metastasis. 2016;33:225-230.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 17]  [Cited by in F6Publishing: 18]  [Article Influence: 2.3]  [Reference Citation Analysis (0)]
77.  Espinet E, Gu Z, Imbusch CD, Giese NA, Büscher M, Safavi M, Weisenburger S, Klein C, Vogel V, Falcone M, Insua-Rodríguez J, Reitberger M, Thiel V, Kossi SO, Muckenhuber A, Sarai K, Lee AYL, Backx E, Zarei S, Gaida MM, Rodríguez-Paredes M, Donato E, Yen HY, Eils R, Schlesner M, Pfarr N, Hackert T, Plass C, Brors B, Steiger K, Weichenhan D, Arda HE, Rooman I, Kopp JL, Strobel O, Weichert W, Sprick MR, Trumpp A. Aggressive PDACs Show Hypomethylation of Repetitive Elements and the Execution of an Intrinsic IFN Program Linked to a Ductal Cell of Origin. Cancer Discov. 2021;11:638-659.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 34]  [Cited by in F6Publishing: 35]  [Article Influence: 11.7]  [Reference Citation Analysis (0)]
78.  Roalsø MTT, Hald ØH, Alexeeva M, Søreide K. Emerging Role of Epigenetic Alterations as Biomarkers and Novel Targets for Treatments in Pancreatic Ductal Adenocarcinoma. Cancers (Basel). 2022;14.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 2]  [Cited by in F6Publishing: 3]  [Article Influence: 3.0]  [Reference Citation Analysis (0)]
79.  Patil S, Steuber B, Kopp W, Kari V, Urbach L, Wang X, Küffer S, Bohnenberger H, Spyropoulou D, Zhang Z, Versemann L, Bösherz MS, Brunner M, Gaedcke J, Ströbel P, Zhang JS, Neesse A, Ellenrieder V, Singh SK, Johnsen SA, Hessmann E. EZH2 Regulates Pancreatic Cancer Subtype Identity and Tumor Progression via Transcriptional Repression of GATA6. Cancer Res. 2020;80:4620-4632.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 27]  [Cited by in F6Publishing: 30]  [Article Influence: 10.0]  [Reference Citation Analysis (0)]
80.  Neesse A, Bauer CA, Öhlund D, Lauth M, Buchholz M, Michl P, Tuveson DA, Gress TM. Stromal biology and therapy in pancreatic cancer: ready for clinical translation? Gut. 2019;68:159-171.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 190]  [Cited by in F6Publishing: 195]  [Article Influence: 48.8]  [Reference Citation Analysis (0)]
81.  Versemann L, Hessmann E, Ulisse M. Epigenetic Therapeutic Strategies to Target Molecular and Cellular Heterogeneity in Pancreatic Cancer. Visc Med. 2022;38:11-19.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 5]  [Cited by in F6Publishing: 4]  [Article Influence: 4.0]  [Reference Citation Analysis (0)]
82.  Pechalrieu D, Etievant C, Arimondo PB. DNA methyltransferase inhibitors in cancer: From pharmacology to translational studies. Biochem Pharmacol. 2017;129:1-13.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 66]  [Cited by in F6Publishing: 54]  [Article Influence: 7.7]  [Reference Citation Analysis (0)]
83.  Ganji C, Farran B. Current clinical trials for epigenetic targets and therapeutic inhibitors for pancreatic cancer therapy. Drug Discov Today. 2022;27:1404-1410.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 2]  [Cited by in F6Publishing: 2]  [Article Influence: 1.0]  [Reference Citation Analysis (0)]
84.  Ettel M, Zhao L, Schechter S, Shi J. Expression and prognostic value of NSD1 and SETD2 in pancreatic ductal adenocarcinoma and its precursor lesions. Pathology. 2019;51:392-398.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 9]  [Cited by in F6Publishing: 9]  [Article Influence: 2.3]  [Reference Citation Analysis (0)]
85.  Ding G, Xu X, Li D, Chen Y, Wang W, Ping D, Jia S, Cao L. Fisetin inhibits proliferation of pancreatic adenocarcinoma by inducing DNA damage via RFXAP/KDM4A-dependent histone H3K36 demethylation. Cell Death Dis. 2020;11:893.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 19]  [Cited by in F6Publishing: 19]  [Article Influence: 6.3]  [Reference Citation Analysis (0)]
86.  Berdasco M, Esteller M. Clinical epigenetics: seizing opportunities for translation. Nat Rev Genet. 2019;20:109-127.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 248]  [Cited by in F6Publishing: 259]  [Article Influence: 64.8]  [Reference Citation Analysis (0)]
87.  Bennett RL, Licht JD. Targeting Epigenetics in Cancer. Annu Rev Pharmacol Toxicol. 2018;58:187-207.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 135]  [Cited by in F6Publishing: 140]  [Article Influence: 23.3]  [Reference Citation Analysis (0)]
88.  Moertl S, Payer S, Kell R, Winkler K, Anastasov N, Atkinson MJ. Comparison of Radiosensitization by HDAC Inhibitors CUDC-101 and SAHA in Pancreatic Cancer Cells. Int J Mol Sci. 2019;20.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 22]  [Cited by in F6Publishing: 22]  [Article Influence: 5.5]  [Reference Citation Analysis (0)]
89.  De Souza C, Chatterji BP. HDAC Inhibitors as Novel Anti-Cancer Therapeutics. Recent Pat Anticancer Drug Discov. 2015;10:145-162.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 86]  [Cited by in F6Publishing: 90]  [Article Influence: 12.9]  [Reference Citation Analysis (0)]
90.  Bian B, Bigonnet M, Gayet O, Loncle C, Maignan A, Gilabert M, Moutardier V, Garcia S, Turrini O, Delpero JR, Giovannini M, Grandval P, Gasmi M, Ouaissi M, Secq V, Poizat F, Nicolle R, Blum Y, Marisa L, Rubis M, Raoul JL, Bradner JE, Qi J, Lomberk G, Urrutia R, Saul A, Dusetti N, Iovanna J. Gene expression profiling of patient-derived pancreatic cancer xenografts predicts sensitivity to the BET bromodomain inhibitor JQ1: implications for individualized medicine efforts. EMBO Mol Med. 2017;9:482-497.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 48]  [Cited by in F6Publishing: 53]  [Article Influence: 8.8]  [Reference Citation Analysis (0)]
91.  Bian B, Juiz NA, Gayet O, Bigonnet M, Brandone N, Roques J, Cros J, Wang N, Dusetti N, Iovanna J. Pancreatic Cancer Organoids for Determining Sensitivity to Bromodomain and Extra-Terminal Inhibitors (BETi). Front Oncol. 2019;9:475.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 24]  [Cited by in F6Publishing: 25]  [Article Influence: 6.3]  [Reference Citation Analysis (0)]
92.  Lu C, Yang D, Sabbatini ME, Colby AH, Grinstaff MW, Oberlies NH, Pearce C, Liu K. Contrasting roles of H3K4me3 and H3K9me3 in regulation of apoptosis and gemcitabine resistance in human pancreatic cancer cells. BMC Cancer. 2018;18:149.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 29]  [Cited by in F6Publishing: 34]  [Article Influence: 6.8]  [Reference Citation Analysis (0)]
93.  Tan N, Wong M, Nannini MA, Hong R, Lee LB, Price S, Williams K, Savy PP, Yue P, Sampath D, Settleman J, Fairbrother WJ, Belmont LD. Bcl-2/Bcl-xL inhibition increases the efficacy of MEK inhibition alone and in combination with PI3 kinase inhibition in lung and pancreatic tumor models. Mol Cancer Ther. 2013;12:853-864.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 58]  [Cited by in F6Publishing: 58]  [Article Influence: 5.8]  [Reference Citation Analysis (0)]
94.  Abulwerdi F, Liao C, Liu M, Azmi AS, Aboukameel A, Mady AS, Gulappa T, Cierpicki T, Owens S, Zhang T, Sun D, Stuckey JA, Mohammad RM, Nikolovska-Coleska Z. A novel small-molecule inhibitor of mcl-1 blocks pancreatic cancer growth in vitro and in vivo. Mol Cancer Ther. 2014;13:565-575.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 136]  [Cited by in F6Publishing: 144]  [Article Influence: 14.4]  [Reference Citation Analysis (0)]
95.  Dawkins JB, Wang J, Maniati E, Heward JA, Koniali L, Kocher HM, Martin SA, Chelala C, Balkwill FR, Fitzgibbon J, Grose RP. Reduced Expression of Histone Methyltransferases KMT2C and KMT2D Correlates with Improved Outcome in Pancreatic Ductal Adenocarcinoma. Cancer Res. 2016;76:4861-4871.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 52]  [Cited by in F6Publishing: 57]  [Article Influence: 8.1]  [Reference Citation Analysis (0)]
96.  Matsuura I, Denissova NG, Wang G, He D, Long J, Liu F. Cyclin-dependent kinases regulate the antiproliferative function of Smads. Nature. 2004;430:226-231.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 376]  [Cited by in F6Publishing: 395]  [Article Influence: 20.8]  [Reference Citation Analysis (0)]
97.  Batchu RB, Qazi AM, Gruzdyn OV, Semaan A, Seward SM, Chamala S, Dhulipala VB, Bouwman DL, Weaver DW, Gruber SA. EZH2-shRNA-mediated upregulation of p21waf1/cip1 and its transcriptional enhancers with concomitant downmodulation of mutant p53 in pancreatic ductal adenocarcinoma. Surgery. 2013;154:739-46; discussion 746.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 5]  [Cited by in F6Publishing: 5]  [Article Influence: 0.5]  [Reference Citation Analysis (0)]
98.  Cheng Y, He C, Wang M, Ma X, Mo F, Yang S, Han J, Wei X. Targeting epigenetic regulators for cancer therapy: mechanisms and advances in clinical trials. Signal Transduct Target Ther. 2019;4:62.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 478]  [Cited by in F6Publishing: 379]  [Article Influence: 94.8]  [Reference Citation Analysis (0)]
99.  Kato S, Schwaederle M, Daniels GA, Piccioni D, Kesari S, Bazhenova L, Shimabukuro K, Parker BA, Fanta P, Kurzrock R. Cyclin-dependent kinase pathway aberrations in diverse malignancies: clinical and molecular characteristics. Cell Cycle. 2015;14:1252-1259.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 39]  [Cited by in F6Publishing: 27]  [Article Influence: 3.9]  [Reference Citation Analysis (0)]
100.  Mody HR, Hung SW, AlSaggar M, Griffin J, Govindarajan R. Inhibition of S-Adenosylmethionine-Dependent Methyltransferase Attenuates TGFβ1-Induced EMT and Metastasis in Pancreatic Cancer: Putative Roles of miR-663a and miR-4787-5p. Mol Cancer Res. 2016;14:1124-1135.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 25]  [Cited by in F6Publishing: 27]  [Article Influence: 3.9]  [Reference Citation Analysis (0)]
101.  Huang L, Holtzinger A, Jagan I, BeGora M, Lohse I, Ngai N, Nostro C, Wang R, Muthuswamy LB, Crawford HC, Arrowsmith C, Kalloger SE, Renouf DJ, Connor AA, Cleary S, Schaeffer DF, Roehrl M, Tsao MS, Gallinger S, Keller G, Muthuswamy SK. Ductal pancreatic cancer modeling and drug screening using human pluripotent stem cell- and patient-derived tumor organoids. Nat Med. 2015;21:1364-1371.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 427]  [Cited by in F6Publishing: 453]  [Article Influence: 56.6]  [Reference Citation Analysis (0)]
102.  Hu W, Jia X, Gao Y, Zhang Q. Chaetospirolactone reverses the apoptotic resistance towards TRAIL in pancreatic cancer. Biochem Biophys Res Commun. 2018;495:621-628.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 3]  [Cited by in F6Publishing: 5]  [Article Influence: 0.8]  [Reference Citation Analysis (0)]
103.  Ashkenazi A. Directing cancer cells to self-destruct with pro-apoptotic receptor agonists. Nat Rev Drug Discov. 2008;7:1001-1012.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 323]  [Cited by in F6Publishing: 335]  [Article Influence: 22.3]  [Reference Citation Analysis (0)]
104.  Chen Y, Ren B, Yang J, Wang H, Yang G, Xu R, You L, Zhao Y. The role of histone methylation in the development of digestive cancers: a potential direction for cancer management. Signal Transduct Target Ther. 2020;5:143.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 27]  [Cited by in F6Publishing: 30]  [Article Influence: 10.0]  [Reference Citation Analysis (0)]