Breast cancer (BC) is the most common malignant tumor among women. There is a pressing demand to develop new therapeutic strategies for advanced BC. In this report, we investigated whether Transglutaminase 2 (TGM2) is involved in BC growth. Moreover, a high expression of TGM2 in BC was found to be correlated with a poor prognosis. Thus, TGM2 might be a prospective therapeutic target in BC. We examined if a small molecule inhibitor of TGM2, GK921, could suppress BC growth. GK921 inhibited TGM2 activity and induced autophagy-dependent cell death in BC cell lines. Additionally, we found that GK921 increased p53 levels, which decreased the expression of mTOR, a classical upstream regulator of autophagy. Finally, we found that down regulation of TGM2 using RNAi activated autophagy. Consistent with these findings, GK921 significantly suppressed breast tumor growth in mouse models, suggesting that TGM2 may be a potential therapeutic target for BC treatment.

Chaperone-mediated autophagy (CMA), a type of selective degradation of cytosolic proteins in lysosomes, is commonly upregulated in cancer cells, contributing to their survival and growth. The lack of a specific target for CMA inhibition has limited CMA blockage to genetic manipulations or global lysosomal function inhibition. Here, using genetic modulation, transcriptional analysis, and functional studies, we demonstrate a regulatory role for the interaction of the retinoic acid receptor alpha (RARα) and its corepressor, the nuclear receptor corepressor 1 (NCoR1), on CMA in non-small cell lung cancer (NSCLC). By targeting the disruption of the NCoR1/RARα complex with a structure-based screening strategy, we identified compound CIM7, a potent and selective CMA inhibitor that has no effect on macroautophagy. CIM7 preferentially inhibits CMA in NSCLC cells over normal cells, reduces tumor growth in NSCLC cells, and demonstrates efficacy in an in vivo xenograft mouse model with no observed toxicity in blood or major tissues. These findings reveal a druggable mechanism for selective CMA inhibition and a first-in-class CMA inhibitor as a potential therapeutic strategy for NSCLC.

Lung cancer continues to be a primary contributor to cancer-related deaths globally, and multidrug resistance (MDR) poses a significant obstacle in its management. Traditional Chinese medicines (TCMs), recognized for their comprehensive therapeutic strategies and low incidence of adverse effects, have garnered attention due to their capacity to mitigate MDR in cancer cells. Nevertheless, deciphering the precise mechanisms through which TCMs reverse MDR in lung cancer presents a substantial scientific challenge. The objective of this review is to examine prevalent manifestations of MDR in lung cancer and underscore recent advancements in understanding how TCMs might surmount this form of resistance. The review begins by investigating the unique characteristics of TCMs and their pivotal function in reversing MDR in lung cancer. Subsequently, it explores various forms of MDR in lung cancer, such as aberrant expression of cell membrane transport proteins, dysregulation of intracellular enzyme systems, disrupted apoptosis, and heightened cellular repair mechanisms, emphasizing their detrimental impact on lung cancer treatment outcomes. Central to this review is a thorough analysis of the intricate mechanisms by which TCMs counteract MDR, along with an assessment of their efficacy in lung cancer therapy. Based on this analysis, the review offers insights into potential future research directions for utilizing TCMs to overcome MDR. This review seeks to provide a thorough examination of the role of TCMs in reversing MDR in lung cancer and to stimulate additional research into their clinical applications.

Post ischemia-reperfusion (I/R) injury, an upregulation in Polymerase I and transcript release factor (PTRF) expression is observed. PTRF is implicated in the regulation of various cellular processes within neuronal cells, thereby exacerbating the deleterious effects of I/R injury. EPIC-1042 is a small molecule pharmacological agent that exhibits specificity in binding to PTRF. Therefore, this study aimed to explore whether EPIC-1042 could be used as a treatment for I/R injury. To achieve this goal, we observed brain injury in mice following EPIC-1042 pre-administration, and then transitioned to therapeutic administration. After observing the pre-protective and therapeutic effects of the drug, proteomic analysis revealed that the expression of TAX1BP1 continued to decline in a time-dependent manner, while EPIC-1042 was able to inhibit this decline. However, the function of TAX1BP1 in ischemic stroke is not yet fully understood. Subsequent experiments confirmed that the addition of EPIC-1042 resulted in an enhancement of mitophagy. Silencing the expression of TAX1BP1 abrogated the drug's effects, indicating that EPIC-1042 exerts a protective function by promoting mitophagy via TAX1BP1 mediation. We further investigated the synergistic effects of EPIC-1042 and edaravone by administering the two drugs in combination, observing an enhanced therapeutic efficacy compared to the administration of each drug alone. Subsequently, we optimized the administration protocol for the two drugs by utilizing liposome encapsulation for both drugs. This approach enabled us to achieve significant therapeutic outcomes while reducing both the dosage and frequency of administration, thereby demonstrating the potential for clinical translation of EPIC-1042.

Lung cancer remains a leading cause of cancer-related mortality worldwide. Its progression is intricately associated with the dynamic regulation of autophagy and RNA-binding proteins (RBPs), which play crucial roles in mRNA stability, alternative splicing, and cellular stress responses.

This review aims to systematically analyze the mechanisms through which RBPs and autophagy contribute to lung cancer progression and explore potential therapeutic strategies targeting these pathways.

We reviewed recent studies on the molecular mechanisms by which RBPs regulate tumor proliferation, metabolic adaptation, and their interaction with autophagy. The review also examines the dual roles of autophagy in lung cancer, highlighting its context-dependent effects on cell survival and death.

The interactions and regulatory networks between RBPs and autophagy involve multiple levels of regulation. RBPs can directly influence autophagy processes and act as microRNA (miRNA) sponges to regulate mRNA stability. The modulation of RBPs affects the expression of autophagy-related genes (ATGs) and autophagosome formation. Additionally, RBPs participate in complex regulatory interactions with non-coding RNAs (ncRNAs), including long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and other proteins.

This review proposes innovative therapeutic strategies that combine RBP-targeting approaches (e.g., small molecule inhibitors, CRISPR gene editing) with autophagy modulators (e.g., mTOR inhibitors, chloroquine) to enhance treatment efficacy. Nanoparticle drug delivery systems and epigenetic regulation offer further opportunities for targeted interventions. This review lays a theoretical foundation for advancing lung cancer research and provides novel insights into synergistic therapies that target both RBPs and autophagy to improve treatment outcomes for lung cancer.

Autophagy plays a complex role in cancer progression, serving as both a tumor suppressor and a promoter, depending on the context. In triple-negative breast cancer (TNBC), a particularly aggressive subtype with limited therapeutic options, autophagy inhibition has emerged as a promising strategy to enhance the efficacy of chemotherapy. This study investigates the synergistic effects of autophagy suppression using LC3 siRNA-loaded "smart" nanoparticles (LC3siRNA-NPs) in combination with doxorubicin (DOX) to overcome chemoresistance in TNBC. We engineered a well-defined copolymer, poly[hexyl methacrylate-co-2-(dimethylamino) ethyl methacrylate-co-trimethylaminoethyl methacrylate iodide], and a PEG heteroarm beta-cyclodextrin (βCD) core star copolymer that delivers LC3 siRNA, effectively silencing the autophagy-related gene LC3. In vitro, the coadministration of LC3siRNA-NPs and DOX significantly inhibited TNBC cell proliferation, migration, and colony formation, while inducing apoptosis more effectively than either treatment alone. Mechanistically, this combination downregulated key oncogenic markers such as PARP, cyclin D1, and Src, enhancing the therapeutic outcome. In vivo, treatment with LC3siRNA-NPs and DOX in a TNBC xenograft model resulted in superior tumor growth suppression compared to that with monotherapy alone. Our findings highlight the potential of autophagy-targeting nanocarriers to improve chemotherapy outcomes and provide an effective approach to TNBC treatment by enhancing chemotherapeutic sensitivity and reducing tumor resistance.

Lung adenocarcinoma (LUAD) continues to be a primary cause of cancer-related mortality globally, highlighting the urgent need for novel insights finto its molecular mechanisms. This study aims to investigate the relationship between gene expression and mitophagy in LUAD, with an emphasis on identifying key biomarkers and elucidating their roles in tumorigenesis and immune cell infiltration.

We utilized datasets GSE151101 and GSE203609 from the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs) associated with lung cancer and mitophagy. DEGs were identified using GEO2R, filtered based on criteria of P < 0.05 and log2 fold change ≥ 1. Subsequently, Weighted Gene Co-expression Network Analysis (WGCNA) was conducted to classify DEGs into modules. Functional annotation of these modules was performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Gene Set Enrichment Analysis (GSEA) was applied to the most relevant module, designated as the greenyellow module. To identify critical biomarkers, machine learning algorithms including Random Forest, Least Absolute Shrinkage and Selection Operator (LASSO) regression, and Support Vector Machine (SVM) were employed. Validation of the findings was conducted using The Cancer Genome Atlas (TCGA) database, Human Protein Atlas (HPA), quantitative PCR (qPCR), and immune cell infiltration analysis via CIBERSORTx.

Our analysis identified 11,012 overlapping DEGs between the two datasets. WGCNA revealed 11 modules, with the green-yellow module exhibiting the highest correlation. Functional enrichment analysis highlighted significant associations with FOXM1 signaling pathways and retinoblastoma in cancer. Machine learning algorithms identified COASY, FTSJ1, and MOGS as pivotal genes. These findings were validated using TCGA data, qPCR experiments, which demonstrated high expression levels in LUAD samples. Immunohistochemistry from HPA confirmed consistency between protein levels and RNA-seq data. Furthermore, pan-cancer analysis indicated that these genes are highly expressed across various cancer types. Immune infiltration analysis suggested significant correlations between these genes and specific immune cell populations.

COASY, FTSJ1 and MOGS have emerged as critical biomarkers in LUAD, potentially influencing tumorigenesis through mitophagy-related mechanisms and immune modulation. These findings provide promising avenues for future research into targeted therapies and diagnostic tools, thereby enhancing LUAD management.

Melanocytes are the source of the skin cancer known as melanoma. It usually affects the viscera, mucous membranes, and skin. Even so, melanoma only makes for 7% of all skin cancer occurrences. By triggering the generation of type I interferons (IFN-I) and inflammatory cytokines upon identifying microbial DNA, the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway promotes anti-microbial innate immunity. A growing body of research indicates that antitumor immunity depends on the cGAS-STING axis being activated. The cGAS-STING-regulated downstream cytokines, particularly IFN-I, act as linkages between adaptive and innate immunity. As a result, an increasing amount of research has concentrated on the synthesis and screening of agonists of the STING pathway. As a result, an increasing amount of research has concentrated on the synthesis and screening of agonists of the STING pathway. The many implications of the cGAS-STING pathway in the pathophysiology and therapy of melanoma are thoroughly examined in this study. Our research highlights the significance of the cGAS-STING pathway in melanoma and identifies it as a key target for boosting immunity against tumors.

Autophagy is a cellular degradation process that plays a crucial role in maintaining metabolic homeostasis under conditions of stress or nutrient deprivation. This process involves sequestering, breaking down, and recycling intracellular components such as proteins, organelles, and cytoplasmic materials. Autophagy also serves as a mechanism for eliminating pathogens and engulfing apoptotic cells. In the absence of stress, baseline autophagy activity is essential for degrading damaged cellular components and recycling nutrients to maintain cellular vitality. The relationship between autophagy and cancer is well-established; however, the biphasic nature of autophagy, acting as either a tumor growth inhibitor or promoter, has raised concerns regarding the regulation of tumorigenesis without inadvertently activating harmful aspects of autophagy. Consequently, elucidating the mechanisms by which autophagy contributes to cancer pathogenesis and the factors determining its pro- or anti-tumor effects is vital for devising effective therapeutic strategies. Furthermore, precision medicine approaches that tailor interventions to individual patients may enhance the efficacy of autophagy-related cancer treatments. To this end, interventions aimed at modulating the fate of tumor cells by controlling or inducing autophagy substrates necessitate meticulous monitoring of these mediators' functions within the tumor microenvironment to make informed decisions regarding their activation or inactivation. This review provides an updated perspective on the roles of autophagy in cancer, and discusses the potential challenges associated with autophagy-related cancer treatment. The article also highlights currently available strategies and identifies questions that require further investigation in the future.

Salamanders demonstrate exceptional resistance to starvation, allowing them to endure extended periods without food in their natural habitats. Although autophagy, a process involving evolutionarily conserved proteins, promotes survival during food scarcity, the specific mechanism by which it contributes to the extreme starvation resistance in newt cells remains unexplored. Our study, using the newt species Pleurodeles waltl, reveals that newt primary fibroblasts maintain constant autophagy activation during prolonged cellular starvation. Unlike normal mammalian fibroblasts, where autophagosome formation increases during acute starvation but returns to baseline levels after extended periods, newt cells maintain elevated autophagosome numbers even 4 d after autophagy initiation, surpassing levels observed in nutrient-rich conditions. Unique P. waltl mTOR orthologs show reduced lysosomal localization compared with mammalian cells in both nutrient-rich and starved states. However, newt cells exhibit dephosphorylation of mTOR substrates under starvation conditions, similar to mammalian cells. These observations suggest that newts may have evolved a distinctive system to balance seemingly conflicting factors: high regenerative capacity and autophagy-mediated survival during starvation.

Small cell lung cancer (SCLC) is an aggressive malignancy characterized by rapid proliferation and high metastatic potential. It is characterized by universal inactivation of and RB1, overexpression of the MYC family and dysregulation of multiple oncogenic signaling pathways. Among different patients, SCLCs are similar at the genetic level but exhibit significant heterogeneity at the molecular level. The classification of SCLC has evolved from a simple neuroendocrine (NE)/non-neuroendocrine (non-NE) classification system to a transcription factor-based molecular subtype system; lineage plasticity adds further complexity and poses challenges for therapeutic development. While SCLC is initially sensitive to platinum-based chemotherapy, resistance develops rapidly, leading to a dismal prognosis. Various antibodies, including PD-1/PD-L1 inhibitors and antibody‒drug conjugates, have been introduced into clinical practice or are being evaluated in clinical trials. However, their therapeutic benefits for SCLC patients remain limited. This review summarizes SCLC carcinogenic mechanisms, tumor heterogeneity, and the immune microenvironment of SCLC, with a focus on recent advances in metastasis and resistance mechanisms. Additionally, the corresponding clinical progress in tackling these challenges is discussed.

Programmed necrosis, a controlled cell death method that bypasses resistance mechanisms that render apoptosis ineffective, is a potential cancer treatment target. Due to their diverse biological activities and low side effects, natural products are being explored as modulators of programmed necrosis pathways. This review highlights the potential of natural compounds to target cancer cells while preserving healthy tissues and their interaction with essential programmed necrosis mechanisms like ferroptosis and necroptosis. Recent developments have identified various types of programmable necrosis, including necroptosis, ferroptosis, pyroptosis, proptosis, mitochondrial permeability transition-driven necrosis, and oncosis. Natural compounds are increasingly being utilized as a primary source of anti-cancer medications, providing new cancer treatments. This review demonstrates the molecular mechanisms behind lipid peroxidation, mixed lineage kinase domain-like protein, and receptor-interacting protein kinases (RIPK1 and RIPK3) inducing cell death. Recent research has identified natural compounds like polyphenols, alkaloids, and terpenoids that can modulate pathways and benefit preclinical cancer models. The review underscores the potential of natural compounds in developing innovative cancer treatments by integrating pharmacology and cellular signaling knowledge. Integrating natural compound studies and programmed necrosis research presents a promising avenue for oncologists to overcome treatment resistance. Natural compounds have shown potential in developing programmed necrosis as a novel cancer treatment approach, enhancing therapeutic effectiveness and minimizing side effects through preclinical research, pharmacology, and molecular biology.

Trametinib, an inhibitor of mitogen-activated extracellular signal-regulated kinases 1/2 (MEK1/2), is used to treat BRAFV600E/K melanoma and non-small-cell lung cancer (NSCLC). Mutant Kirsten rat sarcoma viral oncogene homolog (KRAS) promotes glutamine utilization, therefore, in the present study we investigated the anti-cancer effects of trametinib in combination with V-9302, a glutamine transporter inhibitor, in NSCLC with KRAS mutations. Trametinib in combination with V-9302 exhibited a potent synergistic antitumor effect, inducing cell cycle arrest and pyroptosis. Mechanistically, combination treatment triggered caspase-3 activation and gasdermin E (GSDME) cleavage, as well as elevated lactate dehydrogenase (LDH) and IL-1β levels. Meanwhile, combination treatment reduced cyclin D1 and p-Rb levels and increased p27 expression. Moreover, this combination increased forkhead box class O3a (FOXO3a) levels and decreased forkhead box M1 (FOXM1) expression by regulating the phosphorylation of ERK, Akt, AMPK, and c-Jun N-terminal kinase (JNK). Trametinib in combination with V-9302 increased reactive oxygen species (ROS) generation and reduced glutathione (GSH) synthesis and ATP levels. Furthermore, V-9302 in combination with trametinib inhibited the trametinib-induced autophagy, thereby enhancing pyroptosis in cancer cells. In vivo, the co-administration of trametinib and V-9302 remarkably inhibited tumor growth in a xenograft mouse model compared to each drug alone. Taken together, the combination of trametinib and V-9302 resulted in increased pyroptosis and cell cycle arrest compared to each single agent through regulation of the FOXO3a/FOXM1 axis and autophagy and significantly enhanced antitumor efficacy in vivo. Our results suggest a potential new therapeutic strategy for KRAS-mutant NSCLC using trametinib in combination with glutamine restriction.

Forkhead box (FOX) genes are a family of transcription factors that participate in many biological activities, from early embryogenesis to the formation of organs, and from regulation of glucose metabolism to regulation of longevity. Given the extensive influence in the multicellular process, FOX family proteins are responsible for the progression of many types of cancers, especially lung cancer, breast cancer, prostate cancer, and other cancers. Breast cancer is the most common cancer among women, and 2.3 million women were diagnosed in 2020. So, various drugs targeting the FOX signaling pathway have been developed to inhibit breast cancer progression. While the role of the FOX family gene in cancer development has not received enough attention, discovering more potential drugs targeting the FOX signaling pathway is urgently demanded. Here, we review the main members in the FOX gene family and summarize their signaling pathway, including the regulation of the FOX genes and their effects on breast cancer progression. We hope this review will emphasize the understanding of the role of the FOX gene in breast cancer and inspire the discovery of effective anti-breast cancer medicines targeting the FOX gene in the future.

Autophagy is a conservative process of self degradation, in which abnormal organelles, proteins and other macromolecules are encapsulated and transferred to lysosomes for subsequent degradation. It maintains the intracellular balance, and responds to cellular conditions such as hunger or stress. To date, there are mainly three types of autophagy: macroautophagy, microautophagy and chaperone-mediated autophagy. Autophagy plays a key role in regulating multiple physiological and pathological processes, such as cell metabolism, development, energy homeostasis, cell death and hunger adaptation, and so on. Increasing evidence indicates that autophagy dysfunction participates in many kinds of cancers, such as liver cancer, pancreatic cancer, prostate cancer, and so on. However, the relevant mechanisms are not yet fully understood. Baicalin is a natural flavonoid compound extracted from the traditional Chinese medicine Scutellaria baicalensis. The research has shown that after oral or intravenous administration of baicalin, it is delivered to various organs through the systemic circulation, with the highest volume in the kidneys and lungs. More and more evidence suggests that baicalin has antioxidant, anticancer, anti-inflammatory, anti-apoptotic, immunomodulatory and antiviral effects. Therefore, baicalin plays an important role in various diseases, such as cancers, lung diseases, liver diseases, cardiovascular diseases, ans so on. However, the relevant mechanisms have not yet been fully clear. Recently, increasing evidence indicates that baicalin participates in different cancer by regulating autophagy. Herein, we reviewed the current knowledge about the role and mechanism of baicalin regulation of autophagy in multiple types of cancers to lay the theoretical foundation for future related researches.

Oral squamous cell carcinomas (OSCCs), like several solid tumours, contain heterogeneous subpopulations of a small subset of cancer cells, termed cancer stem cells (CSCs), that are highly relevant to cancer metastasis and invasive properties. CSCs have also shown a high capacity to survive against various stressful environments, such as hypoxia. However, the molecular underpinnings behind the high potential of CSCs to survive under this stress remain unclear. The current study aimed to investigate the significance of autophagy systems in oral CSC maintenance and survival under stress conditions. Human OSCC cell lines OECM-1 and OECM-1 CSCs were cultured in different hypoxic time periods for proliferation and cytotoxicity analyses. The stemness property of CSCs is evaluated by sphere formation, transwell and wound healing assays protein expression of stemness, and epithelial-to-mesenchymal transition markers. Mitochondrial functions, including mitochondrial ROS generation, mitochondria dynamics, mitophagy, and mitochondrial metabolism (glycolysis and oxidative phosphorylation [OXPHOS]) were examined by western blotting, immunohistochemistry, and XF-seahorse assays, respectively. Under hypoxia, oral CSCs showed a higher proliferation rate with increased invasion/migration/EMT properties than OECM-1 cells. Further, hypoxia-induced BNIP3-driven mitophagy was activated in OECM-1 CSCs than in OECM-1 cells, which also triggered a metabolic shift towards OXPHOS, and BNIP3/-L silencing by siRNA significantly attenuated OECM-1 CSCs stemness features. TCGA data analyses also revealed a higher BNIP3 expression in head and neck squamous carcinoma patients' tumour samples associated with lower patient survival. Collectively, our results revealed a BNIP3/-L-driven autophagy contributes to the OECM-1 CSCs stemness features under hypoxia, suggesting a novel therapeutic strategy involving BNIP3 and autophagy inhibition in oral CSCs.

Worldwide, almost 10 million cancer deaths occurred in 2022, a number that is expected to rise to 16.3 million by 2040. Primary prevention has long been acknowledged as a crucial approach to reducing cancer incidence. In fact, between 30 and 50 percent of all tumors are known to be preventable by eating a healthy diet, staying active, avoiding alcohol, smoking, and being overweight. Accordingly, many international organizations have created tumor prevention guidelines, which underlie the importance of following a diet that emphasizes eating plant-based foods while minimizing the consumption of red/processed meat, sugars, processed foods, and alcohol. However, further research is needed to define the relationship between the effect of specific diets or nutritional components on cancer prevention. Interestingly, reductions in food intake and dietetic restrictions can extend the lifespan of yeast, nematodes, flies, and rodents. Despite controversial results in humans, those approaches have the potential to ameliorate health via direct and indirect effects on specific signaling pathways involved in cancer onset. Here, we describe the latest knowledge on the cancer-preventive potential of dietary restrictions and the biochemical processes involved. Molecular, preclinical, and clinical studies evaluating the effects of different fasting strategies will also be reviewed.

Chronic inflammation is a cancer hallmark and chronic exposure to interleukin-1 (IL-1) transforms castration-sensitive prostate cancer (PCa) cells into more fit castration-insensitive PCa cells. p62 is a scaffold protein that protects cells from nutrient deprivation via autophagy and from cytotoxic reactive oxygen via NFκB and NRF2 antioxidant signaling. Herein, we report that the LNCaP PCa cell line acquires high basal accumulation of the p62-KEAP1 complex when chronically exposed to IL-1. p62 promotes non-canonical NRF2 antioxidant signaling by binding and sequestering KEAP1 to the autophagosome for degradation. But despite high basal p62-KEAP1 accumulation, only two of several NRF2-induced genes analyzed, GCLC and HMOX1, showed high basal mRNA levels, suggesting that the high basal p62-KEAP1 accumulation does not result in overall high basal NRF2 activity. Nutrient starvation induces NRF2-dependent GCLC upregulation and HMOX1 repression, and we found that chronic IL-1-exposed LNCaP cells show hypersensitivity to serum starvation-induced GCLC and HMOX1 regulation. Thus, chronic IL-1 exposure affects cell response to nutrient stress. While HMOX1 expression remains NRF2/KEAP1-dependent in chronic IL-1-exposed LNCaP cells, GCLC expression is NRF2/KEAP1-independent. Furthermore, the high basal p62-KEAP1 complex accumulation is not required to regulate GCLC or HMOX1 expression, suggesting cells chronically exposed to IL-1 evolve a novel NRF2-independent role for the p62/KEAP1 axis.

Despite recent breakthroughs in diagnosis and treatment, cancer remains a worldwide health challenge with high mortality. Autophagy plays a major role in the progression and development. Starving cancer cells obtain nutrients through the upregulation of autophagy. Several compounds derived from natural sources, including animals, plants, and microorganisms, have been identified as potential novel anticancer drugs. Spices play an important role in human health and possess many medicinal properties. Our study aimed to identify potential autophagy modulators from panch phoron spices (P5S) through in silico approaches. Herein, we report a structure-based virtual screening of compounds isolated from P5S (i.e., cumin, fenugreek, fennel, black mustard, and black cumin) against the molecular targets of autophagy. Using various computational tools, we attempted to identify potential modulators of autophagy. Among all the screening results (such as binding energy, hydrogen bonding, drug-likeness, bioactivity, ADME properties, and toxicity), P5S, stigmasterol, and tigogenin showed the best drug-like properties and binding affinity toward the selected targets of autophagy. Furthermore, the stability of both complexes was evaluated by performing a 100 ns molecular dynamics simulation (MDS) using Schrodinger's Desmond Module. Our results provide insight into the efficacy of P5S components against cancer. Therefore, targeting autophagy using these molecules may be an effective and potential drug candidate for cancer treatment. In conclusion, stigmasterol and tigogenin may act as potential candidates for anticancer drugs by targeting autophagy.

Prostate cancer is a prevalent malignancy that is frequently managed with radiotherapy. However, resistance to radiotherapy remains a significant challenge in controlling this disease. Early radiotherapy is employed for locally confined prostate cancer (PCa), while recurrent disease post-surgery and metastatic castration-resistant prostate cancer (mCRPC) are treated with late-stage radiotherapy, including radium-223. Combination therapies to integrate radiotherapy and chemotherapy have demonstrated enhanced treatment efficacy. Nonetheless, both modalities can induce severe local and systemic toxicities. Consequently, selectively sensitizing prostate tumors to radiotherapy could improve therapeutic outcomes while minimizing systemic side effects. The mechanisms underlying radioresistance in prostate cancer are multifaceted, including DNA damage repair (DDR) pathways, hypoxia, angiogenesis, androgen receptor (AR) signaling, and immune evasion. The advent of 177Lu-PSMA-617, which was approved in 2022, has shown promise in targeting prostate-specific membrane antigen (PSMA) in advanced prostate cancer. Experimental and clinical studies have yielded promising results in suppressing prostate tumors by targeting these pathways. This paper reviews potential targets for sensitizing prostate tumors to radiotherapy. We discuss cellular and molecular mechanisms contributing to therapy resistance and examine findings from experimental and clinical trials on promising targets and drugs that can be used in combination with radiotherapy.

Rationale: Lung cancer remains a major global health burden with limited therapeutic options. Alternative splicing, a critical post-transcriptional process, contributes to lung cancer progression through autophagy, although the underlying mechanisms remain largely unexplored. This study aims to elucidate the role of DDX24 as a splicing factor that contributes to lung cancer progression via autophagy. Methods: To establish the link between DDX24 and lung cancer progression, we performed colony formation assays, growth curve analyses, and xenograft tumor models in nude mice. Mass spectrometry and RNA sequencing were employed to investigate the involvement of DDX24 in alternative splicing, with a specific focus on the splicing of IKBKG. The mechanisms by which DDX24 regulates autophagy were further explored using co-immunoprecipitation and luciferase reporter assays. Results: The splicing factor DDX24 is significantly elevated in lung cancer tissues. Loss of DDX24 suppresses lung cancer growth by promoting autophagy. We identified DDX24 as a splicing factor that plays critical roles in the regulation of alternative splicing. Mechanistically, DDX24 regulates the alternative splicing of autophagy-related genes, including IKBKG. We demonstrate that DDX24 directly binds to IKBKG pre-mRNA, whereas DDX24 ablation stimulates the generation of the long splicing isoform of IKBKG, thereby promoting autophagy through activating of the NF-kB signaling pathway and the transcription of the BECN1 gene. Functional rescue experiments confirm that the long IKBKG isoform-mediated autophagy confers the anti-tumor effects of DDX24 depletion. In addition, IKBKG-L is positively associated with improved survival in lung cancer patients. Conclusions: This study uncovers a novel regulatory axis involving DDX24, IKBKG splicing, and autophagy in lung cancer. Our findings suggest that targeting DDX24 may represent a promising therapeutic strategy for lung cancer treatment, offering new insights into the molecular underpinnings of this disease.

Macroautophagy/autophagy is a highly conserved evolutionary mechanism involving lysosomes for the degradation of cytoplasmic components including organelles. The constitutive, basal level of autophagy is fundamental for preserving cellular homeostasis; however, alterations in autophagy can cause disease pathogenesis, including cancer. The role of autophagy in cancer is particularly complicated, since this process acts both as a tumor suppressor in precancerous stages but facilitates tumor progression during carcinogenesis and later stages of cancer progression. This shift between anti-tumor and pro-tumor roles may be influenced by genetic and environmental factors modulating key pathways such as those involving autophagy-related proteins, the PI3K-AKT-MTOR axis, and AMPK, which often show dysregulation in tumors. Autophagy regulates various cellular functions, including metabolism of glucose, glutamine, and lipids, cell proliferation, metastasis, and several types of cell death (apoptosis, ferroptosis, necroptosis and immunogenic cell death). These multifaceted roles demonstrate the potential of autophagy to affect DNA damage repair, cell death pathways, proliferation and survival, which are critical in determining cancer cells' response to chemotherapy. Therefore, targeting autophagy pathways presents a promising strategy to combat chemoresistance, as one of the major reasons for the failure in cancer patient treatment. Furthermore, autophagy modulates immune evasion and the function of immune cells such as T cells and dendritic cells, influencing the tumor microenvironment and cancer's biological behavior. However, the therapeutic targeting of autophagy is complex due to its dual role in promoting survival and inducing cell death in cancer cells, highlighting the need for strategies that consider both the beneficial and detrimental effects of autophagy modulation in cancer therapy. Hence, both inducers and inhibitors of autophagy have been introduced for the treatment of cancer. This review emphasizes the intricate interplay between autophagy, tumor biology, and immune responses, offering insights into potential therapeutic approaches that deploy autophagy in the cancer suppression.

Skin flaps are often used for repair and reconstruction, including oral cavity and palate. However, postoperative flap necrosis limited applications. Myrtenol, a plant-derived bicyclic monoterpene, has pharmacological effects including inhibiting apoptosis and promoting autophagy. But any impact on skin flaps survival remains unclear. Thus, we established modified McFarlane flaps on 24 Sprague-Dawley rats and applied myrtenol. They were randomly divided into low-dose myrtenol (L-Myr), high-dose myrtenol (H-Myr), inhibitor and control groups. On postoperative day 7, flap survival rate was increased and Laser Doppler images showed blood circulation improvement under myrtenol treatment. Hematoxylin and eosin staining (H&E) results indicated that it increased micro vessel density (MVD) and decreased neutrophil numbers. Besides, kits detection showed that it improved anti-oxidant stress factors activities and reduced pro-oxidant stress factors contents. Moreover, immunofluorescence and Western blot results demonstrated that it upregulated the expression of pro-angiogenic factors, anti-apoptotic proteins, pro-autophagic proteins, mitogen-activated protein kinase 1/2 (MEK1/2) and extracellular signal-regulated kinases 1/2 (ERK1/2) and downregulated the expression of pro-inflammatory cytokines, pro-apoptotic proteins and anti-autophagic proteins. The specific inhibitor U0126 of MEK/ERK pathway partially reversed these effects. Overall, Myrtenol promoted angiogenesis, reduced oxidative stress, ameliorated inflammation, inhibited apoptosis and upregulated autophagy via MEK/ERK pathway to promote flap survival.

Isorhapontigenin (ISO), an active compound isolated from the Chinese herb Gnetum Cleistostachyum, exhibited strong preventive and therapeutic effects on bladder cancer (BC) both in vitro and in vivo. Our previous studies revealed that ISO-induced autophagy is crucial for its anti-cancer activity. However, the underlying mechanism remains unclear. Here, we showed that BECN1, an important autophagic protein, was induced by ISO treatment and played crucial roles in ISO-induced late phase of LC3B-dependent, and LC3A-independent autophagy, as well as anti-cancer activity. Downregulation of BECN1 was observed in human BCs and BBN-induced mouse invasive BC tissues, whereas co-treatment with ISO completely reversed BECN1 downregulation in BBN-induced mouse invasive BCs. Consistently, ISO treatment significantly increased BECN1 expression in vitro in a dose- and time-dependent manner. Depletion of BECN1 significantly impaired LC3B-dependent autophagy following ISO treatment, as well as abolished the inhibitory effect of ISO on anchorage-independent growth of human BC cells. Mechanistic studies revealed that BECN1 induction was mediated by ISO downregulation of c-Myc, which resulted in miR-613 reduction, in turn leading to increased NCL translation and further promoting NCL binding to BECN1 mRNA, subsequently stabilizing BECN1 mRNA. In conclusion, our results demonstrate that by activating c-Myc/miR-613/NCL axis, ISO treatment results in BECN1 posttranscriptional upregulation, which specifically initiates LC3B-dependent autophagy and anti-cancer activity. Our findings further strengths our application of ISO for therapy of high-grade invasive BC (HGIBC) patients.

Genome-wide association studies identified variants around the BIN1 (bridging integrator 1) gene locus as prominent risk factors for late-onset Alzheimer disease. In the present study, we decreased the expression of BIN1 in mouse hippocampal neurons to investigate its neuronal function. Bin1 knockdown via RNAi reduced the dendritic arbor size in primary cultured hippocampal neurons as well as in mature Cornu Ammonis 1 excitatory neurons. The AAV-mediated Bin1 RNAi knockdown also generated a significant regional volume loss around the injection sites at the organ level, as revealed by 7-Tesla structural magnetic resonance imaging, and an impaired spatial reference memory performance in the Barnes maze test. Unexpectedly, Bin1 knockdown led to concurrent activation of both macroautophagy/autophagy and MTOR (mechanistic target of rapamycin kinase) complex 1 (MTORC1). Autophagy inhibition with the lysosome inhibitor chloroquine effectively mitigated the Bin1 knockdown-induced dendritic regression. The subsequent molecular studydemonstrated that increased expression of ULK3 (unc-51 like kinase 3), which is MTOR-insensitive, supported autophagosome formation in BIN1 deficiency. Reducing ULK3 activity with SU6668, a receptor tyrosine kinase inhibitor, or decreasing neuronal ULK3 expression through AAV-mediated RNAi, significantly attenuated Bin1 knockdown-induced hippocampal volume loss and spatial memory decline. In Alzheimer disease patients, the major neuronal isoform of BIN1 is specifically reduced. Our work suggests this reduction is probably an important molecular event that increases the autophagy level, which might subsequently promote brain atrophy and cognitive impairment through reducing dendritic structures, and ULK3 is a potential interventional target for relieving these detrimental effects.Abbreviations: AV: adeno-associated virus; Aβ: amyloid-β; ACTB: actin, beta; AD: Alzheimer disease; Aduk: Another Drosophila Unc-51-like kinase; AKT1: thymoma viral proto-oncogene 1; AMPK: AMP-activated protein kinase; AP: autophagosome; BafA1: bafilomycin A1; BDNF: brain derived neurotrophic factor; BIN1: bridging integrator 1; BIN1-iso1: BIN1, isoform 1; CA1: cornu Ammonis 1; CA3: cornu Ammonis 3; CLAP: clathrin and adapter binding; CQ: chloroquine; DMEM: Dulbecco's modified Eagle medium; EGFP: enhanced green fluorescent protein; GWAS: genome-wide association study; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MRI: magnetic resonance imaging; MTOR; mechanistic target of rapamycin kinase; MTORC1: MTOR complex 1; PET: positron emission tomography; qRT-PCR: real-time quantitative reverse transcription PCR; ROS: reactive oxygen species; RPS6KB1: ribosomal protein S6 kinase B1; TFEB: transcription factor EB; ULK1: unc-51 like kinase 1; ULK3: unc-51 like kinase 3.

Lipid droplets (LDs) are cellular organelles specialized in the storage and regulating the release of lipids critical for energy metabolism. As investigation on LDs deepens, the complex biological functions of LDs are revealed and their relationships with various diseases such as atherosclerosis, fatty liver, obesity, and cancer are uncovered. Fluorescence-based techniques with simple operations, visible results and high non-invasiveness are ideal tools for investigating LD-related biological processes and diseases. Materials with aggregation-induced emission (AIE) characteristics have emerged as promising candidates for investigating LDs due to their high signal-to-noise ratio (S/N), strong photostability, and large Stokes shift. This review discusses the principles and advantages of LD-targeting AIE probes for imaging LDs, diagnosis of LD-associated diseases including atherosclerotic plaques, liver diseases, acute kidney diseases and cancer, therapies with LD-targeting AIE-active photosensitizers and other relevant fields in the past five years. Through typical examples, we illustrate the status of investigating LD-related imaging, diagnosis of diseases and therapy with AIE materials. This review is expected to attract attentions from scientists with different research backgrounds and contribute to the further development of LD-targeting AIE materials.

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.

Nasopharyngeal carcinoma (NPC), a highly invasive form of head and neck cancer, carries a significant risk of distant metastasis. NPC is particularly prevalent in Asia and has a high incidence in southern China. Cisplatin-diamminedichloroplatinum (DDP), a chemotherapy agent, is commonly employed in NPC treatment. Despite DDP's efficacy, many patients eventually develop resistance to it over the course of their therapy, which significantly hinders treatment outcomes. Cancer-associated fibroblasts (CAFs) are key components of the tumor micro-environment and contribute to tumor progression and chemotherapy resistance. Exosomes secreted by CAFs serve as crucial mediators of intercellular communication and participate in modulating diverse biological processes. This study aimed to explore how exosomes derived from CAFs contribute to DDP resistance in NPC.

An in vitro coculture system was used to simulate the interaction between CAFs and NPC cells, and exosomes secreted by CAFs were isolated and characterized. The expression of autophagy hallmark proteins was detected by Western blot and quantitative real-time polymerase chain reaction. Autophagy intensity was quantified using monodansylcadaverine staining, and cell proliferation was assessed by colony formation assays and methylthiazolyldiphenyl-tetrazolium assays. NPC cells were treated with autophagy inducers (rapamycin), and the expression of Ras homologue enriched in brain (Rheb), mammalian target of rapamycin complex (mTORC1), and UNC51-like kinase was detected. Immunofluorescence was used to determine the cellular localization and expression intensity of mTORC1, and the effect on DDP sensitivity was evaluated through cell proliferation rates. In addition, the exosome-mediated resistance mechanism was further validated using an in vivo xenograft tumor model.

Coculture of CAFs with NPC cells significantly promoted the proliferation of NPC cells (P < 0.01), significantly elevated the IC50 value of DDP (P < 0.01), and elevated the resistance of NPC cells to DDP. CAF-derived exosomes elevated autophagy hallmark proteins light chain 3B-II, Beclin, and increased the autophagy intensity (P < 0.01). CAF-derived exosomes promoted autophagy by inhibiting mTORC1 (P < 0.01). In the in vitro model, exosomes promoted the growth of tumor tissues (P < 0.01), and the inhibition of exosome secretion reversed the promotion effect of autophagy (P < 0.01) and elevated the sensitivity of NPC cells to DDP.

CAF-derived exosomes promote protective autophagy in NPC cells through the Rheb/mTOR axis, and result in DDP resistance in NPC.

Mitochondrial transcription elongation factor (TEFM) is a recently discovered factor involved in mitochondrial DNA replication and transcription. Previous studies have reported that abnormal TEFM expression can disrupt the assembly of mitochondrial respiratory chain and thus mitochondrial function. However, the role of TEFM on Uterine corpus endometrial carcinoma (UCEC) progression remains unclear. The present study aims to investigate the expression of TEFM in tumor tissue of UCEC and the effect of abnormal TEFM expression on malignant phenotype of UCEC cells.

The expressions of TEFM were measured in tumor tissues and cell lines of UCEC by immunohistochemistry, Western blotting, and real-time quantitative PCR assays. Besides, the effects of TEFM knockdown or overexpression on UCEC cell growth, metastasis, apoptosis, and autophagy were also determined using EdU, colony formation, flow cytometry, TUNEL, and transmission electron microscopy assays. Xenograft model was used to confirm the role of TEFM on proliferative potential of UECE cells in vivo.

Our bioinformatics analysis of CPTAC data showed that TEFM is abnormally overexpressed in UCEC and its upregulation was significantly associated with poor survival of patients with UCEC. We found that TEFM upregulation significantly promoted the growth and metastasis of UCEC cells. Mechanically, TEFM upregulation impaired the function of mitochondria, decreased their membrane potential and activated the AKT-NFκB pathway by promoting reactive oxygen species (ROS) production, leading to enhanced intracellular autophagy and thus UCEC growth and metastasis.

This study demonstrates that TEFM positively regulates autophagy to promote the growth and metastasis of UCEC cells, which provides a potential prognostic biomarker and therapeutic target for the treatment of UCEC.

Cancer remains a significant global challenge, and despite the numerous strategies developed to advance cancer therapy, an effective cure for metastatic cancer remains elusive. A major hurdle in treatment success is the ability of cancer cells, particularly cancer stem cells (CSCs), to resist therapy. These CSCs possess unique abilities, including self-renewal, differentiation, and repair, which drive tumor progression and chemotherapy resistance. The resilience of CSCs is linked to certain signaling pathways. Tumors with pathway-dependent CSCs often develop genetic resistance, whereas those with pathway-independent CSCs undergo epigenetic changes that affect gene regulation. CSCs can evade cytotoxic drugs, radiation, and apoptosis by increasing drug efflux transporter activity and activating survival mechanisms. Future research should prioritize the identification of new biomarkers and signaling molecules to better understand drug resistance. The use of cutting-edge approaches, such as bioinformatics, genomics, proteomics, and nanotechnology, offers potential solutions to this challenge. Key strategies include developing targeted therapies, employing nanocarriers for precise drug delivery, and focusing on CSC-targeted pathways such as the Wnt, Notch, and Hedgehog pathways. Additionally, investigating multitarget inhibitors, immunotherapy, and nanodrug delivery systems is critical for overcoming drug resistance in cancer cells.

Hepatocellular carcinoma (HCC), characterized by significant morbidity and mortality rates, poses a substantial threat to human health. The expression of ligands and receptors within the classical and non-classical Wnt signaling pathways plays an important role in HCC. The Wnt signaling pathway is essential for regulating multiple biological processes in HCC, including proliferation, invasion, migration, tumor microenvironment modulation, epithelial-mesenchymal transition (EMT), stem cell characteristics, and autophagy. Molecular agents that specifically target the Wnt signaling pathway have demonstrated significant potential for the treatment of HCC. However, the precise mechanism by which the Wnt signaling pathway interacts with HCC remains unclear. In this paper, we review the alteration of the Wnt signaling pathway in HCC, the mechanism of Wnt pathway action in HCC, and molecular agents targeting the Wnt pathway. This paper provides a theoretical foundation for identifying molecular agents targeting the Wnt pathway in hepatocellular carcinoma.

Autophagy is an essential intracellular degradation system responsible for delivering cytoplasmic components to lysosomes. Within this intricate process, optineurin (OPTN), an autophagy receptor, has attracted extensive attention due to its multifaceted roles in the autophagy process. OPTN is regulated by various posttranslational modifications and actively participates in numerous signaling pathways and cellular processes. By exploring the regulatory mechanism of OPTN posttranslational modification, we can further understand the critical role of protein posttranslational modification in biological progress, such as autophagy. Additionally, OPTN is implicated in many human diseases, including rheumatoid arthritis, osteoporosis, and infectious diseases. And we delve into the inflammatory pathways regulated by OPTN and clarify how it regulates inflammatory diseases and cancer. We aim to enhance the understanding of OPTN's multifaceted functions in cellular processes and its implications in the pathogenesis of inflammatory diseases and cancer.

Cholangiocarcinoma is one of the most lethal human cancers, and chemotherapy failure is a major cause of recurrence and poor prognosis. We previously demonstrated that miR-200 family members are downregulated in clinical samples of cholangiocarcinoma and inhibit cholangiocarcinoma tumorigenesis and metastasis. However, the role of differentially expressed miR-200b-3p in 5-fluorouracil chemosensitivity remains unclear. Here, we examined how miR-200b-3p modulates 5-fluorouracil chemosensitivity in cholangiocarcinoma. We observed that miR-200b-3p was associated with 5-fluorouracil sensitivity in cholangiocarcinoma and increased 5-fluorouracil-induced mitochondrial apoptosis in cholangiocarcinoma cells. Mechanistically, miR-200b-3p suppressed autophagy in cholangiocarcinoma cells to mediate 5-fluorouracil sensitivity. Further, we identified KLF4 as an essential target of miR-200b-3p in cholangiocarcinoma. Notably, the miR-200b-3p/KLF4/autophagy pathway augmented the chemosensitivity of cholangiocarcinoma cells to 5-fluorouracil. Our findings underscore the key role of miR-200b-3p in chemosensitivity to 5-fluorouracil and highlight the miR-200b-3p/KLF4/autophagy axis as a potential therapeutic target for cholangiocarcinoma.

Autophagy is a critical cellular process for degrading damaged organelles and proteins under stressful conditions and has casually been shown to contribute to tumor survival and drug resistance. Sequestosome-1 (SQSTM1/p62) is an autophagy receptor that interacts with its binding partners via the LC3-interacting region (LIR). The p62 protein has been a highly researched target for its critical role in selective autophagy. In this study, we aimed to identify FDA-approved drugs that bind to the LIR motif of p62 and inhibit its LIR function, which could be useful targets for modulating autophagy. To this, the homology model of the p62 protein was predicted using biological data, and docking analysis was performed using Molegro Virtual Docker and PyRx softwares. We further assessed the toxicity profile of the drugs using the ProTox-II server and performed dynamics simulations on the effective candidate drugs identified. The results revealed that the kanamycin, velpatasvir, verteporfin, and temoporfin significantly decreased the binding of LIR to the p62 protein. Finally, we experimentally confirmed that Kanamycin can inhibit autophagy-associated acidic vesicular formation in breast cancer MCF-7 and MDA-MB 231 cells. These repositioned drugs may represent novel autophagy modulators in clinical management, warranting further investigation.

Calreticulin (CALR) is a multifunctional calcium-binding protein. Recent studies have revealed that CALR contributes to tumor development and promotes cancer cell proliferation. However, how CALR affects the development of laryngeal squamous cell carcinoma (LSCC) remains mysterious. Thus, this study aimed to explore the effect of CALR on LSCC development and uncover its underlying mechanisms.

CALR expression in LSCC cell lines and tissues was examined by qRT-PCR and western blot analysis and its functional role was detected via in vivo and in vitro assays. Cell proliferation was discriminated with CCK-8 and colony formation assays, while apoptosis was analyzed using flow cytometry. Autophagy levels were measured via LC3 immunofluorescence, and western blot assay was conducted to assess apoptosis- and autophagy-related proteins. Additionally, a mouse xenograft model was employed to determine the impact of CALR knockdown on tumor growth.

We found that CALR knockdown reduced LSCC cell viability and proliferation while enhancing apoptosis, whereas CALR overexpression showed opposite effects. In vivo experiments verified that CALR knockdown suppressed tumor growth. In addition, elevated CALR expression induced autophagy in LSCC cells, while autophagy inhibitor 3-MA (2.5 mM) reversed the anti-apoptosis effects of CALR overexpression.

Our study identifies CALR as an oncogene in LSCC, where it promotes tumor progression by inducing autophagy and inhibiting apoptosis. Targeting CALR or modulating autophagy may represent novel therapeutic strategies for LSCC.

Autophagy is an intracellular degradation process that sequesters cytoplasmic components in double-membrane vesicles known as autophagosomes, which are degraded upon fusion with lysosomes. This pathway maintains the integrity of proteins and organelles while providing energy and nutrients to cells, particularly under nutrient deprivation. Deregulation of autophagy can cause genomic instability, low protein quality, and DNA damage, all of which can contribute to cancer. Autophagy can also be overactivated in cancer cells to aid in cancer cell survival and drug resistance. Emerging evidence indicates that autophagy has functions beyond cargo degradation, including roles in tumor immunity and cancer stem cell survival. Additionally, autophagy can also influence the tumor microenvironment. This feature warrants further investigation of the role of autophagy in cancer, in which autophagy manipulation can improve cancer therapies, including cancer immunotherapy. This review discusses recent findings on the regulation of autophagy and its role in cancer therapy and drug resistance.