Gastric cancer (GC) is one of the most aggressive malignancies worldwide and is characterized by its poor prognosis and resistance to conventional therapies. Autophagy and long non-coding RNAs (lncRNAs) play critical yet complex roles in GC, functioning as both tumor suppressors and promoters depending on the disease stage and context. Autophagy influences cellular homeostasis and metabolism, whereas lncRNAs regulate gene expression through epigenetic modifications, RNA sponging, and protein interactions. Notably, the interplay between lncRNAs and autophagy modulates tumor progression, metastasis, chemoresistance, and the tumor microenvironment. This study explored the intricate relationship between lncRNAs and autophagy in GC, highlighting their roles in pathogenesis and treatment resistance. By addressing current knowledge gaps and proposing innovative therapeutic strategies, we have emphasized the potential of targeting this dynamic interplay for improved diagnostic and therapeutic outcomes.

Autophagy plays a role in chemotherapy resistance by facilitating cell survival under stress conditions in many malignancies, including ovarian cancers. The use of ascitic fluid to study autophagy biomarkers is an emerging approach, with potential advantages over tissue-based studies in cancer research. This study aimed to standardize reproducible laboratory methods for detecting and quantifying autophagy biomarkers in the ascitic fluid of ovarian cancer patients.

Ascitic fluid samples were analyzed using three techniques in 30 ovarian cancer patients: (1) enzyme-linked immunosorbent assay (ELISA) for Beclin 1, p62/sequestosome 1 (p62/sqstm1), and synaptosomal associated protein 23 (SNAP 23); (2) immunocytochemistry (ICC) for Syntaxin 17 and vesicle-associated membrane protein 8 (VAMP 8) localization; and (3) flow cytometry for epithelial cell identification and Annexin V expression assessment.

We standardized autophagy marker expression in ascitic fluid from ovarian cancer patients. Although the sample size was small, preliminary differences in biomarker expression were observed across disease phases. Beclin 1 levels were elevated in relapsed patients compared to newly diagnosed patients, suggesting potential autophagy activation. Further validation with larger cohorts is needed. ICC revealed heterogeneous expression of Syntaxin 17 and VAMP 8, with variations observed across patient samples. Flow cytometry identified tumor epithelial cells and Annexin V (pro-apoptotic marker) expression in these cells.

Techniques for analyzing autophagy markers in ascitic fluid were successfully standardized. The ascitic fluid analysis offers a non-invasive, accessible method for studying ovarian cancer biology, potentially enhancing understanding and management. Further research with larger cohorts and integration of traditional biomarkers could improve clinical utility in ovarian cancer.

Globally, the incidence and death rates associated with cancer persist in rising, despite considerable advancements in cancer therapy. Although some malignancies are manageable by a mix of chemotherapy, surgery, radiation, and targeted therapy, most malignant tumors either exhibit poor responsiveness to early identification or endure post-treatment survival. The prognosis for prostate cancer (PCa) is unfavorable since it is a perilous and lethal malignancy. The capacity of phytochemical and nutraceutical chemicals to repress oncogenic lncRNAs and activate tumor suppressor lncRNAs has garnered significant attention as a possible strategy to diminish the development, proliferation, metastasis, and invasion of cancer cells. A potential technique to treat cancer and enhance the sensitivity of cancer cells to existing conventional therapies is the use of phytochemicals with anticancer characteristics. Functional studies indicate that lncRNAs modulate drug resistance, stemness, invasion, metastasis, angiogenesis, and proliferation via interactions with tumor suppressors and oncoproteins. Among them, numerous lncRNAs, such as HOTAIR, PlncRNA1, GAS5, MEG3, LincRNA-21, and POTEF-AS1, support the development of PCa through many molecular mechanisms, including modulation of tumor suppressors and regulation of various signal pathways like PI3K/Akt, Bax/Caspase 3, P53, MAPK cascade, and TGF-β1. Other lncRNAs, in particular, MALAT-1, CCAT2, DANCR, LncRNA-ATB, PlncRNA1, LincRNA-21, POTEF-AS1, ZEB1-AS1, SChLAP1, and H19, are key players in regulating the aforementioned processes. Natural substances have shown promising anticancer benefits against PCa by altering essential signaling pathways. The overexpression of some lncRNAs is associated with advanced TNM stage, metastasis, chemoresistance, and reduced survival. LncRNAs possess crucial clinical and transitional implications in PCa, as diagnostic and prognostic biomarkers, as well as medicinal targets. To impede the progression of PCa, it is beneficial to target aberrant long non-coding RNAs using antisense oligonucleotides or small interfering RNAs (siRNAs). This prevents them from transmitting harmful messages. In summary, several precision medicine approaches may be used to rectify dysfunctional lncRNA regulatory circuits, so improving early PCa detection and eventually facilitating the conquest of this lethal disease. Due to their presence in biological fluids and tissues, they may serve as novel biomarkers. Enhancing PCa treatments mitigates resistance to chemotherapy and radiation.

Breast cancer is a heterogeneous disease, with a subpopulation of tumor cells known as breast cancer stem cells (BCSCs) with self-renewal and differentiation abilities that play a critical role in tumor initiation, progression, and therapy resistance. The tumor microenvironment (TME) is a complex area where diverse cancer cells reside creating a highly interactive environment with secreted factors, and the extracellular matrix. Autophagy, a cellular self-digestion process, influences dynamic cellular processes in the tumor TME integrating diverse signals that regulate tumor development and heterogeneity. Autophagy acts as a double-edged sword in the breast TME, with both tumor-promoting and tumor-suppressing roles. Autophagy promotes breast tumorigenesis by regulating tumor cell survival, migration and invasion, metabolic reprogramming, and epithelial-mesenchymal transition (EMT). BCSCs harness autophagy to maintain stemness properties, evade immune surveillance, and resist therapeutic interventions. Conversely, excessive, or dysregulated autophagy may lead to BCSC differentiation or cell death, offering a potential avenue for therapeutic exploration. The molecular mechanisms that regulate autophagy in BCSCs including the mammalian target of rapamycin (mTOR), AMPK, and Beclin-1 signaling pathways may be potential targets for pharmacological intervention in breast cancer. This review provides a comprehensive overview of the relationship between autophagy and BCSCs, highlighting recent advancements in our understanding of their interplay. We also discuss the current state of autophagy-targeting agents and their preclinical and clinical development in BCSCs.

Colorectal cancer (CRC) remains a leading cause of death globally despite the improvements in cancer treatment. Autophagy is an evolutionarily conserved lysosomal-dependent degradation pathway that is critical in maintaining cellular homeostasis. However, in cancer, autophagy may have conflicting functions in preventing early tumour formation versus the maintenance of advanced-stage tumours. Defective autophagy has a broad and dynamic effect not just on cancer cells, but also on the tumour microenvironment which influences tumour progression and response to treatment. To add to the layer of complexity, somatic mutations in CRC including tumour protein p53 (TP53), v-raf murine sarcoma viral oncogene homolog B1 (BRAF), Kirsten rat sarcoma viral oncogene homolog (KRAS), and phosphatase and tensin homolog (PTEN) can render chemoresistance by promoting a pro-survival advantage through autophagy. Recent studies have also reported autophagy-related cell deaths that are distinct from classical autophagy by employing parts of the autophagic machinery, which impacts strategies for autophagy regulation in cancer therapy. This review discusses the molecular processes of autophagy in the evolution of CRC and its role in the tumour microenvironment, as well as prospective therapeutic methods based on autophagy suppression or promotion. It also highlights clinical trials using autophagy modulators for treating CRC, underscoring the importance of autophagy regulation in CRC therapy.

Acute myeloid leukemia (AML), a malignant disorder of the hematopoietic system, arises from leukemic stem cells (LSCs) and is the most prevalent form of blood cancer in adults. This study aimed to evaluate the therapeutic potential of polydatin (PD) in AML through ex vivo and in vivo studies, respectively. This study was prompted by PD's novel role in enhancing tumor apoptosis and modulating autophagy. In vitro studies were conducted using the PD-responsive AML cell line KASUMI-1 and found that PD was able to suppress cell proliferation and induce apoptosis by regulating the autophagy pathway. Subsequently, molecular docking was employed to predict the interaction between PD and Autophagy-related protein 5 (ATG5), a key regulator in the autophagy pathway. It was observed that PD inhibited the ubiquitination of ATG5 and enhanced its protein stability, leading to an increase in ATG5 protein levels and subsequent activation of the autophagy pathway (see in Abstract Graphed). The effectiveness and safety of PD in treating AML were confirmed through in vivo experiments using a mouse transplant tumor model, yielding definitive results. Collectively, these results suggest that PD is a promising candidate for the early therapeutic intervention of AML, with a strong potential for clinical application.

Lung inflammation as a result of exposure to toxicants is a major pathological problem. Autophagy (AP) is a process of cell self-digestion and can be disrupted by environmental toxicants, leading to oxidative stress, inflammation and cellular damage. Bryophyllum pinnatum (Lam.) Oken has been used in folklore medicine to manage pathological abnormalities, including inflammation, but mechanisms remain unclear. This work investigated the effects of Bryophyllum pinnatum ethanol leaf extract (BP) on dysfunctional AP in the lungs of Wistar rats exposed to zinc oxide nanoparticles (ZONPs). The experimental rats were orally administered ZONPs for seven days (10 mg/kg). Some exposed rats were post-treated with BP (62.5 and 125 mg/kg) through oral gavage. Oxidative stress, inflammation, and apoptotic and autophagic parameters were assessed using biochemical assay and gene expression methods. Several indices of pulmonary damage were also evaluated. PCR analysis suggested that ZONP downregulated the expression of pro-autophagy-related genes (Beclin 2, ATG5, DAPK, and FOXP3) and upregulated the expression of the TNF-alpha, NF-Kb, LC3 and Bcl2 genes. In contrast, BP significantly (p < 0.0001) reversed ZONP-induced pulmonary toxicity and oxidative stress. It reduced MDA levels and increased SOD, CAT, GSH and GPxD activities. BP significantly (p < 0.0001) downregulated the expressions of proinflammatory genes (IL-6 and JNK) and upregulated the expressions of IL-10, CAT and SOD genes in ZONP-exposed rats. BP restored the lung's histoarchitectural structure after ZNOP-induced distortion. The results suggested that BP has antioxidant and anti-inflammatory properties, and could effectively restore ZNOP-induced dysfunctional AP in the lungs of Wistar rats.

Toxicity assessments of pollutants often overlook the impact of environmental factors like hypoxia, which can alter chemical toxicity with unexpected consequences. In this study, Mugilogobius chulae, an estuarine fish, was used to investigate the effects of hypoxia (H), aspirin (ASA), and their combination (H_ASA) exposure over 24, 72, and 168 h. We employed RNA-seq analysis, expression of key gene expression profiling, enzymatic activity assays, and histopathological and ultrastructural examinations of liver tissue to explore the effects and mechanisms of ASA-coupled hypoxia exposure in fish. Results showed that glycolysis was inhibited, and lipolysis was enhanced in ASA/H_ASA groups. The PPAR signaling pathway was activated, increasing fatty acid β-oxidation and lipophagy to mitigate energy crisis. Both ASA and H_ASA exposures induced p53 expression and inhibited the TOR pathway to combat environmental stress. However, a greater energy demand and heightened sensitivity to ASA were observed in H_ASA compared to ASA exposure. Disruptions in energy and detoxification pathways led to increased stress responses, including enhanced antioxidant activities, autophagy, and apoptotic events, as observed in organelle structures. Overall, sub-chronic H_ASA exposure caused liver injury in M. chulae by affecting energy metabolism, antioxidant regulation, and autophagy processes. This study highlights the influence of hypoxia on ASA toxicity in fish, providing valuable insights for ecological risk assessment of NSAIDs.

From the perspective of circular economy, it is extremely useful to recycle waste products for human health applications. Among the health-beneficial properties of bioactive phyto-compounds, grape pomace represents a precious source of bioactive molecules with potential antitumor properties. Here, we describe the effects of a Sicilian grape pomace hydroalcoholic extract (HE) in colon and breast cancer cells. The characterization of HE composition revealed the predominance of anthoxanthins and phenolic acids. HE treatment was more effective in reducing the viability of colon cancer cells, while breast cancer cells appeared more resistant. Indeed, while colon cancer cells underwent apoptosis, as shown by DNA fragmentation, caspase-3 activation, and PARP1 degradation, breast cancer cells seemed to not undergo apoptosis. To elucidate the underlying mechanisms, reactive oxygen species (ROS) were evaluated. Interestingly, ROS increased in both cell lines but, while in colon cancer, cells' ROS rapidly increased and progressively diminished over time, in breast cancer, cells' ROS increase was persistent up to 24 h. This effect was correlated with the induction of pro-survival autophagy, demonstrated by autophagosomes formation, autophagic markers increase, and protection by the antioxidant NAC. The autophagy inhibitor bafilomycin A1 significantly increased the HE effects in breast cancer cells but not in colon cancer cells. Overall, our data provide evidence that HE efficacy in tumor cells depends on a balance between ROS-mediated autophagy and apoptosis. Therefore, inhibiting pro-survival autophagy may be a tool to target those cells that appear more resistant to the effect of HE.

Hepatocellular carcinoma (HCC), the primary form of liver cancer, is the third leading cause of cancer-related death globally. Hernandonine is a natural alkaloid derived from Hernandia nymphaeifolia that has been shown to exert various biological functions. In a previous study, hernandonine was shown to suppress the proliferation of several solid tumor cell lines without affecting normal human cell lines. However, little is known about the effect of hernandonine on HCC. Therefore, this study aimed to investigate the effect and mechanism of hernandonine on HCC in relation to autophagy. We found that hernandonine inhibited HCC cell growth in vitro and in vivo. In addition, hernandonine elicited autophagic cell death and DNA damage in HCC cells. RNA-seq analysis revealed that hernandonine upregulated p53 and Hippo signaling pathway-related genes in HCC cells. Small RNA interference of p53 resulted in hernandonine-induced autophagic cell death attenuation. However, inhibition of YAP sensitized HCC cells to hernandonine by increasing the autophagy induction. This is the first study to illustrate the complex involvement of p53 and YAP in the hernandonine-induced autophagic cell death in human HCC cells. Our findings provide novel evidence for the potential of hernandonine as a therapeutic agent for HCC treatment.

Besides producing cellular energy, mitochondria are crucial in controlling oxidative stress and modulating cellular metabolism, particularly under stressful conditions. A key aspect of this regulatory role involves the recycling process of autophagy, which helps to sustain energy homeostasis. Autophagy, a lysosome-dependent degradation pathway, plays a fundamental role in maintaining cellular homeostasis by degrading damaged organelles and misfolded proteins. In the context of tumor formation, autophagy significantly influences cancer metabolism and chemotherapy resistance, contributing to both tumor suppression and surveillance. This review focuses on the relationship between mitochondria and autophagy, specifically in the context of cancer progression. Investigating the interaction between autophagy and mitochondria reveals new possibilities for cancer treatments and may result in the development of more effective therapies targeting mitochondria, which could have significant implications for cancer treatment. Additionally, this review highlights the increasing understanding of autophagy's role in tumor development, with a focus on modulating mitochondrial function and autophagy in both pre-clinical and clinical cancer research. It also explores the potential for developing more-targeted and personalized therapies by investigating autophagy-related biomarkers.

A convergent strategy for the first total synthesis of the lipopeptide bacilotetrin C has been developed. The key features of this synthesis include Crimmins acetate aldol, Steglich esterification, and macrolactamization. Twenty-nine variants of the natural product were prepared following a systematic structure-activity relationship study, where some of the designed analogues showed promising cytotoxic effects against multiple human carcinoma cell lines. The most potent analogue exhibited a ∼37-fold enhancement in cytotoxicity compared to bacilotetrin C in a triple-negative breast cancer (MDA-MB-231) cell line at submicromolar doses. The study further revealed that some of the analogues induced autophagy in cancer cells to the point of their demise at doses much lower than those of known autophagy-inducing peptides. The results demonstrated that the chemical synthesis of bacilotetrin C with suitable improvisation plays an important role in the development of novel anticancer chemotherapeutics, which would allow future rational design of novel autophagy inducers on this template.

Autophagy is a cytoplasmic defense mechanism that cells use to break and reprocess their intracellular components. This utilization of autophagy is regarded as a savior in nutrient-deficient and other stressful conditions. Hence, autophagy keeps contact with and responds to miscellaneous cellular tensions and diverse pathways of signal transductions, such as growth signaling and cellular death. Importantly, autophagy is regarded as an effective tumor suppressor because regular autophagic breakdown is essential for cellular maintenance and minimizing cellular damage. However, paradoxically, autophagy has also been observed to promote the events of malignancies. This review discussed the dual role of autophagy in cancer, emphasizing its influence on tumor survival and progression. Possessing such a dual contribution to the malignant establishment, the prevention of autophagy can potentially advocate for the advancement of malignant transformation. In contrast, for the context of the instituted tumor, the agents of preventing autophagy potently inhibit the advancement of the tumor. Key regulators, including calpain 1, mTORC1, and AMPK, modulate autophagy in response to nutritional conditions and stress. Oncogenic mutations like RAS and B-RAF underscore autophagy's pivotal role in cancer development. The review also delves into autophagy's context-dependent roles in tumorigenesis, metastasis, and the tumor microenvironment (TME). It also discusses the therapeutic effectiveness of autophagy for several cancers. The recent implication of autophagy in the control of both innate and antibody-mediated immune systems made it a center of attention to evaluating its role concerning tumor antigens and treatments of cancer.

Around 1 in 7 men will be diagnosed with prostate cancer during their lifetime. Many strides have been made in the understanding and treatment of this malignancy over the years, however, despite this; treatment resistance and disease progression remain major clinical concerns. Recent evidence indicate that autophagy can affect cancer formation, progression, and therapeutic resistance. Autophagy is an evolutionarily conserved process that can remove unnecessary or dysfunctional components of the cell as a response to metabolic or environmental stress. Due to the emerging importance of autophagy in cancer, targeting autophagy should be considered as a potential option in disease management. In this review, along with exploring the advances made on understanding the role of autophagy in prostate carcinogenesis and therapeutics, we will critically consider the conflicting evidence observed in the literature and suggest how to obtain stronger experimental evidence, as the application of current findings in clinical practice is presently not viable.

Basidalin, isolated from the basidiomycete Leucoagaricus naucina, has previously demonstrated antibacterial and antitumor properties against murine cancer cells in vivo, but its effects on human cancer cells remain unknown. In this study, we found that basidalin possesses antiproliferative activity against human cancer cell lines. To elucidate the antiproliferative mechanism of basidalin, we focused on autophagy. Treatment with basidalin led to an increase in LC3-II expression level, and accelerated autophagic flux through an mTOR-independent pathway. Moreover, according to the structure-activity relationship analysis-including newly synthesized basidalin analogs-the formyl group, not the amino group, contributes to the antiproliferative activities of basidalin against human cancer cells. Additionally, the antiproliferative activity of basidalin analogs was strongly correlated with autophagy-inducing activity, indicating that basidalin exhibits antiproliferative activity through autophagy induction. These data suggest that basidalin, characterized by its ability to upregulate autophagic flux, emerges as a novel anticancer drug.

Naphthylisoquinoline (NIQ) alkaloids are rising as a promising class of secondary metabolites with pharmaceutical potential. NF-κB has already been recognized as a significant modulator of cancer proliferation and drug resistance. We have previously reported the mechanisms behind the cytotoxic effect of dioncophylline A, an NIQ monomer, in leukemia cells. In the current study, we have investigated the cytotoxic effect of jozimine A2, an NIQ dimer, on leukemia cells in comparison to a second, structurally unsymmetric dimer, michellamine B. To this end, molecular docking was applied to predict the binding affinity of the dimers towards NF-κB, which was then validated through microscale thermophoresis. Next, cytotoxicity assays were performed on CCRF-CEM cells and multidrug-resistant CEM/ADR5000 cells following treatment. Transcriptome analysis uncovered the molecular networks affected by jozimine A2 and identified the cell cycle as one of the major affected processes. Cell death modes were evaluated through flow cytometry, while angiogenesis was measured with the endothelial cell tube formation assay on human umbilical vein endothelial cells (HUVECs). The results indicated that jozimine A2 bound to NF-κB, inhibited its activity and prevented its translocation to the nucleus. In addition, jozimine A2 induced cell death through apoptosis and prevented angiogenesis. Our study describes the cytotoxic effect of jozimine A2 on leukemia cells and explains the interactions with the NF-κB signaling pathway and the anticancer activity.

Autophagy plays a vital role in sustaining cellular homeostasis and its alterations have been implicated in the etiology of many diseases. Drugs development targeting autophagy began decades ago and hundreds of agents were developed, some of which are licensed for the clinical usage. However, no existing intervention specifically aimed at modulating autophagy is available. The obstacles that prevent drug developments come from the complexity of the actual impact of autophagy regulators in disease scenarios. With the development and application of new technologies, several promising categories of compounds for autophagy-based therapy have emerged in recent years. In this paper, the autophagy-targeted drugs based on their targets at various hierarchical sites of the autophagic signaling network, e.g., the upstream and downstream of the autophagosome and the autophagic components with enzyme activities are reviewed and analyzed respectively, with special attention paid to those at preclinical or clinical trials. The drugs tailored to specific autophagy alone and combination with drugs/adjuvant therapies widely used in clinical for various diseases treatments are also emphasized. The emerging drug design and development targeting selective autophagy receptors (SARs) and their related proteins, which would be expected to arrest or reverse the progression of disease in various cancers, inflammation, neurodegeneration, and metabolic disorders, are critically reviewed. And the challenges and perspective in clinically developing autophagy-targeted drugs and possible combinations with other medicine are considered in the review.

Modifications of epigenetic factors affect our lives and can give important information regarding one's state of health. In cancer, epigenetic modifications play a crucial role, as they influence various programmed cell death types. The purpose of this review is to investigate how epigenetic modifications, such as DNA methylation, histone modifications, and non-coding RNAs, influence various cell death processes in suppressing or promoting cancer development. Autophagy and apoptosis are the most investigated programmed cell death modes, as based on the tumor stage these cell death types can either promote or prevent cancer evolution. Therefore, our discussion focuses on how epigenetic modifications affect autophagy and apoptosis, as well as their diagnostic and therapeutical potential in combination with available chemotherapeutics. Additionally, we summarize the available data regarding the role of epigenetic modifications on other programmed cell death modes, such as ferroptosis, necroptosis, and parthanatos in cancer and discuss current advancements.

Cancer has become a global public health problem and its harmful effects have received widespread attention. Conventional treatments such as surgical resection, radiotherapy and other techniques are applicable to clinical practice, but new drugs are constantly being developed and other therapeutic approaches, such as immunotherapy are being applied. In addition to studying the effects on individual tumor cells, it is important to explore the role of tumor microenvironment on tumor cell development since tumor cells do not exist alone but in the tumor microenvironment. In the tumor microenvironment, tumor cells are interconnected with other stromal cells and influence each other, among which tumor-associated macrophages (TAMs) are the most numerous immune cells. At the same time, it was found that cancer cells have different levels of autophagy from normal cells. In cancer therapy, the occurrence of autophagy plays an important role in promoting tumor cell death or inhibiting tumor cell death, and is closely related to the environment. Therefore, elucidating the regulatory role of autophagy between TAMs and tumor cells may be an important breakthrough, providing new perspectives for further research on antitumor immune mechanisms and improving the efficacy of cancer immunotherapy.

Cancer is one of the greatest dangers to human wellbeing and survival. A key barrier to effective cancer therapy is development of resistance to anti‑cancer medications. In cancer cells, the AAA+ ATPase family member thyroid hormone receptor interactor 13 (TRIP13) is key in promoting treatment resistance. Nonetheless, knowledge of the molecular processes underlying TRIP13‑based resistance to anticancer therapies is lacking. The present study evaluated the function of TRIP13 expression in anticancer drug resistance and potential methods to overcome this resistance. Additionally, the underlying mechanisms by which TRIP13 promotes resistance to anticancer drugs were explored, including induction of mitotic checkpoint complex surveillance system malfunction, promotion of DNA repair, the enhancement of autophagy and the prevention of immunological clearance. The effects of combination treatment, which include a TRIP13 inhibitor in addition to other inhibitors, were discussed. The present study evaluated the literature on TRIP13 as a possible target and its association with anticancer drug resistance, which may facilitate improvements in current anticancer therapeutic options.

Autophagy is a vital cellular process that functions to degrade and recycle damaged organelles into basic metabolites. This allows a cell to adapt to a diverse range of challenging conditions. Autophagy assists in maintaining homeostasis, and it is tightly regulated by the cell. The disruption of autophagy has been associated with many diseases, such as neurodegenerative disorders and cancer. This review will center its discussion on providing an in-depth analysis of the current molecular understanding of autophagy and its relevance to brain tumors. We will delve into the current literature regarding the role of autophagy in glioma pathogenesis by exploring the major pathways of JAK2/STAT3 and PI3K/AKT/mTOR and summarizing the current therapeutic interventions and strategies for glioma treatment. These treatments will be evaluated on their potential for autophagy induction and the challenges associated with their utilization. By understanding the mechanism of autophagy, clinical applications for future therapeutics in treating gliomas can be better targeted.

Lung cancer accounts for the highest number of deaths among men and women worldwide. Although extensive therapies, either alone or in conjunction with some specific drugs, continue to be the principal regimen for evolving lung cancer, significant improvements are still needed to understand the inherent biology behind progressive inflammation and its detection. Unfortunately, despite every advancement in its treatment, lung cancer patients display different growth mechanisms and continue to die at significant rates. Autophagy, which is a physiological defense mechanism, serves to meet the energy demands of nutrient-deprived cancer cells and sustain the tumor cells under stressed conditions. In contrast, autophagy is believed to play a dual role during different stages of tumorigenesis. During early stages, it acts as a tumor suppressor, degrading oncogenic proteins; however, during later stages, autophagy supports tumor cell survival by minimizing stress in the tumor microenvironment. The pivotal role of the IL6-IL17-IL23 signaling axis has been observed to trigger autophagic events in lung cancer patients. Since the obvious roles of autophagy are a result of different immune signaling cascades, systems biology can be an effective tool to understand these interconnections and enhance cancer treatment and immunotherapy. In this review, we focus on how systems biology can be exploited to target autophagic processes that resolve inflammatory responses and contribute to better treatment in carcinogenesis.

Historical and demographical human cohorts of populations exposed to famine, as well as animal studies, revealed that exposure to food deprivation is associated to lasting health-related effects for the exposed individuals, as well as transgenerational effects in their offspring that affect their diseases' risk and overall longevity. Autophagy, an evolutionary conserved catabolic process, serves as cellular response to cope with nutrient starvation, allowing the mobilization of an internal source of stored nutrients and the production of energy. We review the evidence obtained in multiple model organisms that support the idea that autophagy induction, including through dietary regimes based on reduced food intake, is in fact associated to improved health span and extended lifespan. Thereafter, we expose autophagy-induced chromatin remodeling, such as DNA methylation and histone posttranslational modifications that are known heritable epigenetic marks, as a plausible mechanism for transgenerational epigenetic inheritance of hunger.