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Liquid biopsy is a minimally invasive method that uses biofluid samples instead of tissue samples for cancer diagnosis. Exosomes are small extracellular vesicles secreted by donor cells and act as mediators of intercellular communication in human health and disease. Due to their important roles, exosomes have been considered as promising biomarkers for liquid biopsy. However, traditional methods for exosome isolation and cargo detection methods are time-consuming and inefficient, limiting their practical application. In the past decades, many new strategies, such as microfluidic chips, nanowire arrays and electrochemical biosensors, have been proposed to achieve rapid, accurate and high-throughput detection and analysis of exosomes. In this review, we discussed about the new advance in exosome-based liquid biopsy technology, including isolation, enrichment, cargo detection and analysis approaches. The comparison of currently available methods is also included. Finally, we summarized the advantages and limitations of the present strategies and further gave a perspective to their future translational use. [ABSTRACT FROM AUTHOR]

Background: Phytochemicals possess a wide range of anti‐tumor properties, including the modulation of autophagy and regulation of programmed cell death. Autophagy is a critical process in cellular homeostasis and its dysregulation is associated with several pathological conditions, such as cancer, neurodegenerative diseases, and diabetes. In cancer, autophagy plays a dual role by either promoting tumor growth or suppressing it, depending on the cellular context. During autophagy, autophagosomes engulf cytoplasmic components such as proteins and organelles. LC3‐II (microtubule‐associated protein 1 light chain 3‐II) is an established marker of autophagosome formation, making it central to autophagy monitoring in mammals. Objective: To explore the regulatory role of phytochemicals in LC3‐mediated autophagy and their potential therapeutic impact on cancer. The review emphasizes the involvement of autophagy in tumor promotion and suppression, particularly focusing on autophagy‐related signaling pathways like oxidative stress through the NRF2 pathway, and its implications for genomic stability in cancer development. Methods: The review focuses on a comprehensive analysis of bioactive compounds including Curcumin, Celastrol, Resveratrol, Kaempferol, Naringenin, Carvacrol, Farnesol, and Piperine. Literature on these compounds was examined to assess their influence on autophagy, LC3 expression, and tumor‐related signaling pathways. A systematic literature search was conducted across databases including PubMed, Scopus, and Web of Science from inception to 2023. Studies were selected from prominent databases, focusing on their roles in cancer diagnosis and therapeutic interventions, particularly in relation to LC3‐mediated mechanisms. Results: Phytochemicals have been shown to modulate autophagy through the regulation of LC3‐II levels and autophagic flux in cancer cells. The interaction between autophagy and other cellular pathways such as oxidative stress, inflammation, and epigenetic modulation highlights the complex role of autophagy in tumor biology. For instance, Curcumin and Resveratrol have been reported to either induce or inhibit autophagy depending on cancer type, influencing tumor progression and therapeutic responses. Conclusion: Targeting autophagy through LC3 modulation presents a promising strategy for cancer therapy. The dual role of autophagy in tumor suppression and promotion, however, necessitates careful consideration of the context in which autophagy is induced or inhibited. Future research should aim to delineate these context‐specific roles and explore how phytochemicals can be optimized for therapeutic efficacy. Novel therapeutic strategies should focus on the use of bioactive compounds to fine‐tune autophagy, thereby maximizing tumor suppression and inducing programmed cell death in cancer cells. [ABSTRACT FROM AUTHOR]

Enforcing a well-differentiated state on cells requires tumor suppressor p53 activation as a key player in apoptosis induction and well differentiation. In addition, recent investigations showed a significant correlation between poorly differentiated status and higher expression of NANOG. Inducing the expression of NANOG and decreasing p53 level switch the status of liver cancer cells from well differentiated to poorly status. In this review, we highlighted p53 and NANOG cross-talk in hepatocellular carcinoma (HCC) which is regulated through mitophagy and makes it a novel molecular target to attenuate cancerous phenotype in the management of this tumor. [ABSTRACT FROM AUTHOR]

Autophagy is an intracellular process that targets various cargos for degradation, including members of the cGAS-STING signaling cascade. cGAS-STING senses cytosolic double-stranded DNA and triggers an innate immune response through type I interferons. Emerging evidence suggests that autophagy plays a crucial role in regulating and fine-tuning cGAS-STING signaling. Reciprocally, cGAS-STING pathway members can actively induce canonical as well as various noncanonical forms of autophagy, establishing a regulatory network of feedback mechanisms that alter both the cGAS-STING and the autophagic pathway. The crosstalk between autophagy and the cGAS-STING pathway impacts a wide variety of cellular processes such as protection against pathogenic infections as well as signaling in neurodegenerative disease, autoinflammatory disease and cancer. Here we provide a comprehensive overview of the mechanisms involved in autophagy and cGAS-STING signaling, with a specific focus on the interactions between the two pathways and their importance for cancer. [ABSTRACT FROM AUTHOR]

Autophagy is a cellular self-degradation process that plays a crucial role in maintaining metabolic functions in cells and organisms. Dysfunctional autophagy has been linked to various diseases, including cancer. In cancer, dysregulated autophagy is closely associated with the development of cancer and drug resistance, and it can have both oncogenic and oncostatic effects. Research evidence supports the connection between m6A modification and human diseases, particularly cancer. Abnormalities in m6A modification are involved in the initiation and progression of cancer by regulating the expression of oncogenes and oncostatic genes. There is an interaction between m6A modification and autophagy, both of which play significant roles in cancer. However, the molecular mechanisms underlying this relationship are still unclear. m6A modification can either directly inhibit autophagy or promote its initiation, but the complex relationship between m6A modification, autophagy, and cancer remains poorly understood. Therefore, this paper aims to review the dual role of m6A and autophagy in cancer, explore the impact of m6A modification on autophagy regulation, and discuss the crucial role of the m6A modification-autophagy axis in cancer progression and treatment resistance. [ABSTRACT FROM AUTHOR]

Cancer cells can alter their metabolism to meet energy and molecular requirements due to unfavorable environments with oxygen and nutritional deficiencies. Therefore, metabolic reprogramming is common in a tumor microenvironment (TME). Aryl hydrocarbon receptor (AhR) is a ligand-activated nuclear transcription factor, which can be activated by many exogenous and endogenous ligands. Multiple AhR ligands can be produced by both TME and tumor cells. By attaching to various ligands, AhR regulates cancer metabolic reprogramming by dysregulating various metabolic pathways, including glycolysis, lipid metabolism, and nucleotide metabolism. These regulated pathways greatly contribute to cancer cell growth, metastasis, and evading cancer therapies; however, the underlying mechanisms remain unclear. Herein, we review the relationship between TME and metabolism and describe the important role of AhR in cancer regulation. We also focus on recent findings to discuss the idea that AhR acts as a receptor for metabolic changes in tumors, which may provide new perspectives on the direction of AhR research in tumor metabolic reprogramming and future therapeutic interventions. [ABSTRACT FROM AUTHOR]

Transcription factor BTB domain and CNC homology 1 (BACH1) belongs to the Cap 'n' Collar and basic region Leucine Zipper (CNC-bZIP) family. BACH1 is widely expressed in mammalian tissues, where it regulates epigenetic modifications, heme homeostasis, and oxidative stress. Additionally, it is involved in immune system development. More importantly, BACH1 is highly expressed in and plays a key role in numerous malignant tumors, affecting cellular metabolism, tumor invasion and metastasis, proliferation, different cell death pathways, drug resistance, and the tumor microenvironment. However, few articles systematically summarized the roles of BACH1 in cancer. This review aims to highlight the research status of BACH1 in malignant tumor behaviors, and summarize its role in immune regulation in cancer. Moreover, this review focuses on the potential of BACH1 as a novel therapeutic target and prognostic biomarker. Notably, the mechanisms underlying the roles of BACH1 in ferroptosis, oxidative stress and tumor microenvironment remain to be explored. BACH1 has a dual impact on cancer, which affects the accuracy and efficiency of targeted drug delivery. Finally, the promising directions of future BACH1 research are prospected. A systematical and clear understanding of BACH1 would undoubtedly take us one step closer to facilitating its translation from basic research into the clinic. [ABSTRACT FROM AUTHOR]

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Organoids are established through in vitro 3D culture, and they can mimic the structure and physiological functions of organs or tissues in vivo. Organoids have attracted much attention in recent years. They can provide a reliable technology platform for cancer research and treatment and are a valuable preclinical model for academic research and personalized medicine. A number of studies have confirmed that organoids have great application prospects in new drug development, drug screening, tumour mechanism research, and precision medicine. In this review, we mainly focus on recent advances in the application of organoids in cancer research. We also discussed the opportunities and challenges facing organoids, hoping to indicate directions for the development of organoids in the future. [ABSTRACT FROM AUTHOR]

Macroautophagy/autophagy is a catabolic process by which cytosolic content is engulfed, degraded and recycled. It has been implicated as a critical pathway in advanced stages of cancer, as it maintains tumor cell homeostasis and continuous growth by nourishing hypoxic or nutrient-starved tumors. Autophagy also supports alternative cellular trafficking pathways, providing a mechanism of non-canonical secretion of inflammatory cytokines. This opens a significant therapeutic opportunity for using autophagy inhibitors in cancer and acute inflammatory responses. Here we developed a high throughput compound screen to identify inhibitors of protein-protein interaction (PPI) in autophagy, based on the protein-fragment complementation assay (PCA). We chose to target the ATG12-ATG3 PPI, as this interaction is indispensable for autophagosome formation, and the analyzed structure of the interaction interface predicts that it may be amenable to inhibition by small molecules. We screened 41,161 compounds yielding 17 compounds that effectively inhibit the ATG12-ATG3 interaction in the PCA platform, and which were subsequently filtered by their ability to inhibit autophagosome formation in viable cells. We describe a lead compound (#189) that inhibited GFP-fused MAP1LC3B/LC3B (microtubule associated protein 1 light chain 3 beta) puncta formation in cells with IC50 value corresponding to 9.3 μM. This compound displayed a selective inhibitory effect on the growth of autophagy addicted tumor cells and inhibited secretion of IL1B/IL-1β (interleukin 1 beta) by macrophage-like cells. Compound 189 has the potential to be developed into a therapeutic drug and its discovery documents the power of targeting PPIs for acquiring specific and selective compound inhibitors of autophagy. Abbreviations: ANOVA: analysis of variance; ATG: autophagy related; CQ: chloroquine; GFP: green fluorescent protein; GLuc: Gaussia Luciferase; HEK: human embryonic kidney; IL1B: interleukin 1 beta; LPS: lipopolysaccharide; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; PCA: protein-fragment complementation assay; PDAC: pancreatic ductal adenocarcinoma; PMA: phorbol 12-myristate 13-acetate; PPI: protein-protein interaction. VCL: vinculin. [ABSTRACT FROM AUTHOR]

Cancer cells reprogram their metabolism to support their growth. Since the discovery of the Warburg effect, several other metabolic alterations and metabolites have been described in cancer cells, including lactate, glutamine, and lipid metabolism reprogramming. Together these alterations provide rapidly dividing tumor cells with metabolic intermediates needed for nucleotide, protein, and fatty acid biosynthesis. MicroRNAs are a class of small non-coding RNAs involved in the regulation of virtually all biological pathways. Altered microRNA expression patterns are associated with the onset and development of several diseases, including cancer. Tumor suppressor microRNAs targeting molecules involved in tumor metabolism are frequently downregulated in cancers. Therefore, microRNAs can serve as potential tumor biomarkers and also represent interesting therapeutic targets. This review summarizes recent findings about microRNAs involved in the regulation of tumor metabolism. [ABSTRACT FROM AUTHOR]

Autophagy plays a complex role in several cancer types, including endocrine-dependent cancers, by fueling cellular metabolism and clearing damaged substrates. This conserved recycling process has a dual function across tumor types where it can be tumor suppressive at early stages but tumor promotional in established disease. This review highlights the controversial roles of autophagy in endocrine-dependent tumors regarding cancer initiation, tumorigenesis, metastasis, and treatment response. We summarize clinical trial results thus far and highlight the need for additional mechanistic, preclinical, and clinical studies in endocrine-dependent tumors, particularly in breast cancer and prostate cancer. [ABSTRACT FROM AUTHOR]

Autophagy is a lysosomal degradation system of cytoplasmic components that contributes to cellular homeostasis through the turnover of various biomolecules and organelles, often in a selective manner. Autophagy is closely related to cancer, but its roles in cancer are complicated. It works as either a promoter or suppressor, depending on the stage and type of cancer. In this review, we briefly summarize the basic mechanisms of autophagy and describe the complicated roles of autophagy in cancer. Moreover, we summarize the clinical trials of autophagy inhibitors targeting cancer and the development of more specific autophagy inhibitors for future clinical application. [ABSTRACT FROM AUTHOR]

Background: Autophagy is a lysosome-mediated catabolic process that maintains cell homeostasis and survival. It occurs not only in normal cells such as cardiac muscle cells, neurons, and pancreatic acinar cells but also in various benign and malignant tumors. The abnormal level of intracellular autophagy is closely related to multiple pathophysiological processes, including aging, neurodegeneration, infectious diseases, immune disorders, and cancer. Autophagy mainly plays a dual role in life and death by regulating cell survival, proliferation, and death, thus being involved in the occurrence, development, and treatment of cancer. It is also involved in chemotherapy resistance by a dual role, since it not only promotes the occurrence of drug resistance but also reverses it. Previous findings suggest that the regulation of autophagy can be used as an effective strategy in tumor therapy. Summary: Recent studies found that small molecules from natural products and their derivatives exert anticancer activity by regulating the level of autophagy in tumor cells. Key Messages: Therefore, this review article describes the mechanism of autophagy, the role of autophagy in normal cells and tumor cells, and the research progress on the anticancer molecular mechanism of targets regulating cell autophagy. The aim is to provide a theoretical basis for developing autophagy inhibitors or activators to improve anticancer efficacy. [ABSTRACT FROM AUTHOR]

Background: Erythroderma is an inflammatory skin condition that causes extensive erythema and skin scaling amounting ≥90% of the body surface area. This retrospective cohort study describes the prevalence of malignancy‐associated erythroderma in a single centre where there was concerted effort to systematically offer malignancy screens to all adult erythroderma patients above the age of 65 years. Methods: Clinical charts were reviewed for all adult inpatients and outpatients with erythroderma who attended the National University Hospital (NUH) from 1 July 2019 to 31 December 2021. Data collected included patient demographics, clinical findings, laboratory investigations, disease‐specific investigations such as endoscopic procedures and biopsies, follow‐up duration and mortality data. Results: Seventy‐four patients were analysed. The median age of the patients was 73 years old (interquartile range: 59–81 years old). An underlying dermatosis was the most common cause of erythroderma—63 patients having atopic dermatitis/asteatotic eczema or psoriasis. Three patients had erythroderma from drug eruptions, and 1 patient had chronic actinic dermatitis. Four patients had associated malignancies (5.4%). Half of our patients completed further evaluation for malignancy (52.7%). The rest had either declined or were eventually unable to complete the investigations. There was a higher prevalence of associated malignancy (7.8%) in elderly patients above 65 years old. Conclusion: When compared to existing literature, our cohort reflects a higher observed occurrence of malignancy in association with erythroderma. As delays in evaluation for underlying malignancy could result in potentially deleterious outcomes, it is prudent to consider systematic screening for malignancy in high‐risk populations such as elderly erythroderma patients. [ABSTRACT FROM AUTHOR]

Background: Autophagy related protease 4B (ATG4B) is a protease required for autophagy processing, which is strongly implicated in cancer progression. Phosphorylation of ATG4B is crucial for activation of its protease activity. However, little is known about the relationship of ATG4B and its phosphorylated form at Ser 383 and 392 sites (pS383/392-ATG4B), with clinical outcomes, particularly in colorectal cancer (CRC). Methods: The ATG4B gene expression in CRC patients was obtained from The Cancer Genome Atlas (TCGA) database to analyze its clinical relevance. Tissue microarrays composed of 118 CRC patient specimens were used to determine the associations of ATG4B and pS383/392-ATG4B protein levels with prognosis. The biological functions of ATG4B in CRC cells were inspected with cell proliferation, mobility and spheroid culture assays. Results: ATG4B gene expression was elevated in tumor tissues of CRC patients compared to that in adjacent normal tissues and high level of ATG4B expression was associated with poor survival. Similarly, protein levels of ATG4B and pS383/392-ATG4B were highly correlated with worse overall survival and disease-free survival. Stratification analysis results showed that high level of ATG4B had significantly higher risk of mortality in males and elderly patients compared to those female patients and patients 60 years or younger. In contrast, multivariate Cox's regression analysis indicated that high level of pS383/392-ATG4B was significantly linked to unfavorable overall survival and disease-free survival of males and elderly patients, whereas, it had no correlation with female patients and patients 60 years or younger. Moreover, high level of ATG4B was positively associated with increased mortality risk in patients with advanced AJCC stages (III and IV) and lymph node invasion (N1 and N2) for both overall survival and disease-free survival. Nevertheless, high level of pS383/392-ATG4B was positively correlated with increased mortality risk in patients with early AJCC stages (I and II) and without lymph node invasion (N0). In addition, silencing ATG4B attenuated migration, invasion, and further enhanced the cytotoxic effects of chemotherapeutic drugs in two and three-dimensional cultures of CRC cells. Conclusions: Our results suggest that ATG4B and pS383/392-ATG4B might be suitable biomarkers and therapeutic targets for CRC. [ABSTRACT FROM AUTHOR]

In order to better understand the interplay between ferroptosis and autophagy, enhance the interpretation of the crosstalk between these two forms of regulated cell death, develop the effective pharmacological mechanisms for cancer treatment, discover novel biomarkers for better diagnostic, and envisage the future hotspots of the research on ferroptosis and autophagy, we harnessed bibliometric tools to study the articles published from 2012 to 2022 on the relationship between ferroptosis and autophagy. Web of Science Core Collection (WOSCC) database was used to conduct a comprehensive search and analysis of articles in this field from January 1, 2012, to September 1, 2022. The Citespace 6.1.R2 software and VOS viewer 6.1.8 software were utilized to analyze the overall structure of the network, network clusters, links between clusters, key nodes or pivot points, and pathways. A total of 756 articles associated with the crosstalk between ferroptosis and autophagy were published in 512 journals by 4183 authors in 980 organizations from 55 countries or regions. The distribution of countries and organizations was demonstrated using CiteSpace and VOS viewer. The top three countries with the most articles were China (n = 511), United States (n = 166), and Germany (n = 37). The most productive institutions were Guangzhou Medical University and Central South University (n = 42), but their centralities were relatively low, which values were respective 0.04 and 0.03. Kang and Tang published the most articles related to ferroptosis and autophagy (n = 49), followed by Jiao Liu (n = 22), Guido Kroemer (n = 20), and Daniel Klionsky (n = 12). Published studies on ferroptosis and asthma have the most cited counts. The top three keywords with the highest frequencies were autophagy (n = 283), cell death (n = 243), and oxidative stress (n = 165). Our results provide insights into the development of recognition related to the crosstalk between ferroptosis and autophagy, and the current molecular crosslinked mechanisms in the context of common signal transduction pathways or affecting cellular environment to induce the adaptive stress response and to activate the particular form of regulated cell death (RCD), and the development of cancer treatment based on novel targets and signaling regulatory networks provided by ferroptosis and autophagy. [ABSTRACT FROM AUTHOR]

Objectives To explore the survival and risk factors for cancer occurrence after SLE (SLE-CA). Methods Patients with cancer diagnosed after SLE in Peking Union Medical College Hospital between January 2006 and September 2017 were recruited and followed. Data regarding medication-related and disease-related factors and survival were collected and compared with matched controls. Logistic regressions were applied to identify risk factors. The Kaplan–Meier method with a log-rank test was performed to evaluate survival. Results Forty-five SLE-CA patients and 128 controls were included, with the most common cancer site being the female genital system. SLE-CA patients were exposed to a higher cumulative dosage of CYC, with less mucocutaneous and haematologic involvement and higher anti-dsDNA positivity. At the time of cancer diagnosis, SLE-CA patients had lower SLEDAI 2000 (SLEDAI-2K), tended to achieve Definitions of Remission in SLE remission and minimal disease activity, but had higher SLICC/ACR Damage Index. Multivariable analysis identified high dosage of CYC [odds ratio (OR) 1.027, 95% CI 1.008, 1.046; P  = 0.005] and low SLEDAI-2K at cancer diagnosis (OR 0.756, 95% CI 0.579, 0.986; P  = 0.039) as risk factors. Mucocutaneous (OR 0.330, 95% CI 0.110, 0.991; P  = 0.048) and haematologic involvement (OR 0.304, 95% CI 0.103, 0.902; P  = 0.032) were negatively associated with cancer occurrence after SLE. The 5- and 10-year survival rates in SLE-CA patients were 95.2% and 92.1%, respectively. No significant difference of survival was observed between SLE-CA patients and controls (P  = 0.177). Conclusion High dosage of CYC and disease-related factors (low SLEDAI-2K, less mucocutaneous and haematologic involvement) were related factors for cancer occurrence after SLE, while no survival difference was observed. [ABSTRACT FROM AUTHOR]

Autophagy is a highly conservative self-degradative process. It aims at elimination-impaired proteins and cellular organelles. Previous research confirmed the autophagy role in cancer pathogenesis. This article discusses the role of autophagy in the development of AML. Autophagy seems to be a 'double-sword' mechanism, hence, either its suppression or induction could promote neoplasm growth. This mechanism could also be the aim of the 'molecular targeted therapy.' Chemo- and radiotherapy induce cellular stress in neoplasm cells with subsequent autophagy suppression. Simultaneously, it is claimed that the autophagy suppression increases chemosensitivity 'in neoplastic cells. Some agents, like bortezomib, in turn could promote autophagy process, e.g. in AML (acute myeloid leukemia). However, currently there are not many studies focusing on the role of autophagy in patients suffering for AML. In this review, we summarize the research done so far on the role of autophagy in the development of AML. The analysis of autophagy genes expression profiling in AML could be a relevant factor in the diagnostic process and treatment 'individualization.' Autophagy modulation seems to be a relevant target in the oncological therapy – it could limit disease progression and increase the effectiveness of treatment. [ABSTRACT FROM AUTHOR]

Cancer is a heterogeneous disease characterized by various genetic and phenotypic aberrations. Cancer cells undergo genetic modifications that promote their proliferation, survival, and dissemination as the disease progresses. The unabated proliferation of cancer cells incurs an enormous energy demand that is supplied by metabolic reprogramming. Cancer cells undergo metabolic alterations to provide for increased energy and metabolite requirement; these alterations also help drive the tumor progression. Dysregulation in glucose uptake and increased lactate production via "aerobic glycolysis" were described more than 100 years ago, and since then, the metabolic signature of various cancers has been extensively studied. However, the extensive research in this field has failed to translate into significant therapeutic intervention, except for treating childhood-ALL with amino acid metabolism inhibitor L-asparaginase. Despite the growing understanding of novel metabolic alterations in tumors, the therapeutic targeting of these tumor-specific dysregulations has largely been ineffective in clinical trials. This chapter discusses the major pathways involved in the metabolism of glucose, amino acids, and lipids and highlights the inter-twined nature of metabolic aberrations that promote tumorigenesis in different types of cancer. Finally, we summarise the therapeutic interventions which can be used as a combinational therapy to target metabolic dysregulations that are unique or common in blood, breast, colorectal, lung, and prostate cancer. [ABSTRACT FROM AUTHOR]

Autophagy is a catabolic process that captures cellular waste and degrades them in the lysosome. The main functions of autophagy are quality control of cytosolic proteins and organelles, and intracellular recycling of nutrients in order to maintain cellular homeostasis. Autophagy is upregulated in many cancers to promote cell survival, proliferation, and metastasis. Both cell‐autonomous autophagy (also known as tumor autophagy) and non‐cell‐autonomous autophagy (also known as host autophagy) support tumorigenesis through different mechanisms, including inhibition of p53 activation, sustaining redox homeostasis, maintenance of essential amino acids levels in order to support energy production and biosynthesis, and inhibition of antitumor immune responses. Therefore, autophagy may serve as a tumor‐specific vulnerability and targeting autophagy could be a novel strategy in cancer treatment. [ABSTRACT FROM AUTHOR]

Autophagy is a catabolic process in which an organism responds to its nutrient or metabolic emergencies. It involves the degradation of cytoplasmic proteins and organelles by forming double-membrane vesicles called "autophagosomes." They sequester cargoes, leading them to degradation in the lysosomes. Although autophagy acts as a protective mechanism for maintaining homeostasis through cellular recycling, it is ostensibly a cause of certain cancers, but a cure for others. In other words, insufficient autophagy, due to genetic or cellular dysfunctions, can lead to tumorigenesis. However, many autophagy modulators are developed for cancer therapy. Diverse nanoparticles have been documented to induce autophagy. Also, the highly stable nanoparticles show blockage to autophagic flux. In this review, we revealed a general mechanism by which autophagy can be induced or blocked via nanoparticles as well as several studies recently performed to prove the stated fact. In addition, we have also elucidated the paradoxical roles of autophagy in cancer and how their differential role at different stages of various cancers can affect its treatment outcomes. And finally, we summarize the breakthroughs in cancer disease treatments by using metallic, polymeric, and liposomal nanoparticles as potent autophagy modulators. [ABSTRACT FROM AUTHOR]

Hypoxia is a common feature of solid tumors and is associated with increased tumor progression, resistance to therapy and increased metastasis. Hence, tumor hypoxia is a prognostic factor independent of treatment modality. To survive hypoxia, cells activate macroautophagy/autophagy. Paradoxically, in several cancer types, mutations or loss of essential autophagy genes have been reported that are associated with earlier onset of tumor growth. However, to our knowledge, the phenotypic and therapeutic consequences of autophagy deficiency have remained unexplored. In this study, we determined autophagy-defects in head and neck squamous cell carcinoma (HNSCC) and observed that expression of ATG12 (autophagy related 12) was lost in 25%-40% of HNSCC. In line, ATG12 loss is associated with absence of hypoxia, as determined by pimonidazole immunohistochemistry. Hence, ATG12 loss is associated with improved prognosis after therapy in two independent HNSCC cohorts and 7 additional cancer types. In vivo, ATG12 targeting resulted in decreased hypoxia tolerance, increased necrosis and sensitivity of the tumor to therapy, but in vitro ATG12-deficient cells displayed enhanced survival in nutrient-rich culture medium. Besides oxygen, delivery of glucose was hampered in hypoxic regions in vivo, which increases the reliance of cells on other carbon sources (e.g., L-glutamine). We observed decreased intracellular L-glutamine levels in ATG12-deficient cells during hypoxia and increased cell killing after L-glutamine depletion, indicating a central role for ATG12 in maintaining L-glutamine homeostasis. Our results demonstrate that ATG12low tumors represent a phenotypically different subtype that, due to the lowered hypoxia tolerance, display a favorable outcome after therapy. Abbreviations: ARCON:accelerated radiotherapy with carbogen and nicotinamide; ATG: autophagy related; BrdUrd: bromodeoxyuridine; CA9/CAIX: carbonic anhydrase 9; HIF1A/HIF1α: hypoxia inducible factor 1 subunit alpha; HNSCC: head and neck squamous cell carcinoma; HPV: human papilloma virus; HR: hazard ratio; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MEF: mouse embryonic fibroblast; mRNA: messenger ribonucleic acid; PCR: polymerase chain reaction; SLC2A1/GLUT1: solute carrier family 2 member 1; TCGA: the Cancer Genome Atlas; TME: tumor microenvironment; UTR: untranslated region; VEGF: vascular endothelial growth factor [ABSTRACT FROM AUTHOR]

Autophagy is a cellular degradative pathway that plays diverse roles in maintaining cellular homeostasis. Cellular stress caused by starvation, organelle damage, or proteotoxic aggregates can increase autophagy, which uses the degradative capacity of lysosomal enzymes to mitigate intracellular stresses. Early studies have shown a role for autophagy in the suppression of tumorigenesis. However, work in genetically engineered mouse models and in vitro cell studies have now shown that autophagy can be either cancer‐promoting or inhibiting. Here, we summarize the effects of autophagy on cancer initiation, progression, immune infiltration, and metabolism. We also discuss the efforts to pharmacologically target autophagy in the clinic and highlight future areas for exploration. [ABSTRACT FROM AUTHOR]

Cancer is one of the leading causes of death, with a heavy socio-economical burden for countries. Despite the great advances that have been made in the treatment of cancer, chemotherapy is still the most common method of treatment. However, many side effects, including hepatotoxicity, renal toxicity, and cardiotoxicity, limit the efficacy of conventional chemotherapy. Over recent years, natural products have attracted attention as therapeutic agents against various diseases, such as cancer. Resveratrol (RES), a natural polyphenol occurring in grapes, nuts, wine, and berries, exhibited potential for preventing and treating various cancer types. RES also ameliorates chemotherapy-induced detrimental effects. Furthermore, RES could modulate apoptosis and autophagy as the main forms of cancer cell deaths by targeting various signaling pathways and up/downregulation of apoptotic and autophagic genes. This review will summarize the anti-cancer effects of RES and focus on the fundamental mechanisms and targets for modulating apoptosis and autophagy by RES. [ABSTRACT FROM AUTHOR]

Autophagy is an intracellular catabolic process that degrades cytoplasmic components for recycling in response to stressed conditions, such as nutrient deprivation. Dysregulation of autophagy is associated with various diseases, including cancer. Although autophagy plays dichotomous and context‐dependent roles in cancer, evidence has emerged that cancer cells exploit autophagy for metabolic adaptation. Autophagy is upregulated in many cancer types through tumor cell‐intrinsic proliferation demands and the hypoxic and nutrient‐limited tumor microenvironment (TME). Autophagy‐induced breakdown products then fuel into various metabolic pathways to supply tumor cells with energy and building blocks for biosynthesis and survival. This bidirectional regulation between autophagy and tumor constitutes a vicious cycle to potentiate tumor growth and therapy resistance. In addition, the pro‐tumor functions of autophagy are expanded to host, including cells in TME and distant organs. Thus, inhibition of autophagy or autophagy‐mediated metabolic reprogramming may be a promising strategy for anticancer therapy. Better understanding the metabolic rewiring mechanisms of autophagy for its pro‐tumor effects will provide insights into patient treatment. [ABSTRACT FROM AUTHOR]

Purpose: Autophagy and EMT (epithelial–mesenchymal transition) are the two principal biological processes and ideal therapeutic targets during cancer development. Autophagy, a highly conserved process for degrading dysfunctional cellular components, plays a dual role in tumors depending on the tumor stage and tissue types. The EMT process is the transition differentiation from an epithelial cell to a mesenchymal-like cell and acquiring metastatic potential. There is evidence that the crosstalk between autophagy and EMT is complex in cancer. In recent years, more studies have shown that long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) are involved in autophagy, EMT, and their crosstalk. Therefore, accurate understanding of the regulatory mechanisms of lncRNAs and miRNAs in autophagy, EMT and their interactions is crucial for the clinical management of cancers. Methods: An extensive literature search was conducted on the Google Scholar and PubMed databases. The keywords used for the search included: autophagy, EMT, crosstalk, lncRNAs, miRNAs, cancers, diagnostic biomarkers, and therapeutic targets. This search provided relevant articles published in peer-reviewed journals until 2021. Data from these various studies were extracted and used in this review. Results: The results showed that lncRNAs/miRNAs as tumor inhibitors or tumor inducers could regulate autophagy, EMT, and their interaction by regulating several molecular signaling pathways. The lncRNAs/miRNAs involved in autophagy and EMT processes could have potential uses in cancer diagnosis, prognosis, and therapy. Conclusion: Such information could help find and develop lncRNAs/miRNAs based new tools for diagnosing, prognosis, and creating anti-cancer therapies. [ABSTRACT FROM AUTHOR]

To investigate the effect of antimalarials on cancer risk in patients with systemic lupus erythematosus (SLE). PubMed, EMBASE, Web of Science, and the Cochrane Library were searched from their inception to October 3, 2020. Relative risk (RR) with 95% confidence intervals (CI) was used to evaluate the results. Subgroup analyses were used to assess heterogeneity. A funnel plot was used to explore publication bias. STATA was applied for all analyses. A total of nine studies consisted of four nested case–control, two case–cohort and three cohort studies were included. The results showed that antimalarials might reduce the risk of cancer in SLE (RR = 0.68, 95%CI: 0.55–0.85). In the subgroup analysis of four nested case–control and two case–cohort studies, the pooled RR was estimated as 0.69 (95% CI: 0.60–0.80). In four studies about hydroxychloroquine, the pooled RR was estimated as 0.70 (95% CI: 0.53–0.93). Antimalarials might reduce the risk of cancer in SLE among the Asian population (RR = 0.66; 95% CI: 0.49–0.88) (I2 = 43.1%, p =.173). And the consistent result was also found in SLE from multiple centres (RR = 0.72; 95%CI: 0.60–0.87) (I2 = 0%, p =.671). On disease course- and comorbidities-matched studies, the pooled RRs were 0.69 (95% CI: 0.52–0.93) and 0.59 (95% CI: 0.46–0.75), respectively. Results of this meta-analysis showed that antimalarial drugs might be protective factors for cancer in SLE. Hydroxychloroquine might be a protective factor for cancer in SLE patients. Antimalarials might be protective factors for cancer in SLE. Hydroxychloroquine might be a protective factor for cancer in SLE patients. The first article to perform the meta-analysis of antimalarial drugs on the risk of cancer in SLE patients. [ABSTRACT FROM AUTHOR]

The complex and adaptive nature of malignant neoplasm constitute a major challenge for the development of effective anti-oncogenic therapies. Emerging evidence has uncovered the pivotal functions exerted by the small leucine-rich proteoglycans, decorin and biglycan, in affecting tumor growth and progression. In their soluble forms, decorin and biglycan act as powerful signaling molecules. By receptor-mediated signal transduction, both proteoglycans modulate key processes vital for tumor initiation and progression, such as autophagy, inflammation, cell-cycle, apoptosis, and angiogenesis. Despite of their structural homology, these two proteoglycans interact with distinct cell surface receptors and thus modulate distinct signaling pathways that ultimately affect cancer development. In this review, we summarize growing evidence for the complex roles of decorin and biglycan signaling in tumor biology and address potential novel therapeutic implications. [ABSTRACT FROM AUTHOR]

Terpenoids are the largest class of natural products, most of which are derived from plants. Amongst their numerous biological properties, their anti-tumor effects are of interest for they are extremely diverse which include anti-proliferative, apoptotic, anti-angiogenic, and anti-metastatic activities. Recently, several in vitro and in vivo studies have been dedicated to understanding the 'terpenoid induced autophagy' phenomenon in cancer cells. Light has already been shed on the intricacy of apoptosis and autophagy relationship. This latter crosstalk is driven by the delicate balance between activating or silencing of certain proteins whereby the outcome is expressed via interrelated signaling pathways. In this review, we focus on nine of the most studied terpenoids and on their cell death and autophagic activity. These terpenoids are grouped in three classes: sesquiterpenoid (artemisinin, parthenolide), diterpenoids (oridonin, triptolide), and triterpenoids (alisol, betulinic acid, oleanolic acid, platycodin D, and ursolic acid). We have selected these nine terpenoids among others as they belong to the different major classes of terpenoids and our extensive search of the literature indicated that they were the most studied in terms of autophagy in cancer. These terpenoids alone demonstrate the complexity by which these secondary metabolites induce autophagy via complex signaling pathways such as MAPK/ERK/JNK, PI3K/AKT/mTOR, AMPK, NF-kB, and reactive oxygen species. Moreover, induction of autophagy can be either destructive or protective in tumor cells. Nevertheless, should this phenomenon be well understood, we ought to be able to exploit it to create novel therapies and design more effective regimens in the management and treatment of cancer. [ABSTRACT FROM AUTHOR]

Autophagy is a core molecular pathway for the preservation of cellular and organismal homeostasis. Pharmacological and genetic interventions impairing autophagy responses promote or aggravate disease in a plethora of experimental models. Consistently, mutations in autophagy‐related processes cause severe human pathologies. Here, we review and discuss preclinical data linking autophagy dysfunction to the pathogenesis of major human disorders including cancer as well as cardiovascular, neurodegenerative, metabolic, pulmonary, renal, infectious, musculoskeletal, and ocular disorders. [ABSTRACT FROM AUTHOR]

Mitophagy is a selective form of macroautophagy in which dysfunctional and damaged mitochondria can be efficiently degraded, removed and recycled through autophagy. Selective removal of damaged or fragmented mitochondria is critical to the functional integrity of the entire mitochondrial network and cells. In past decades, numerous studies have shown that mitophagy is involved in various diseases; however, since the dual role of mitophagy in tumour development, mitophagy role in tumour is controversial, and further elucidation is needed. That is, although mitophagy has been demonstrated to contribute to carcinogenesis, cell migration, ferroptosis inhibition, cancer stemness maintenance, tumour immune escape, drug resistance, etc. during cancer progression, many research also shows that to promote cancer cell death, mitophagy can be induced physiologically or pharmacologically to maintain normal cellular metabolism and prevent cell stress responses and genome damage by diminishing mitochondrial damage, thus suppressing tumour development accompanying these changes. Signalling pathway-specific molecular mechanisms are currently of great biological significance in the identification of potential therapeutic targets. Here, we review recent progress of molecular pathways mediating mitophagy including both canonical pathways (Parkin/PINK1- and FUNDC1-mediated mitophagy) and noncanonical pathways (FKBP8-, Nrf2-, and DRP1-mediated mitophagy); and the regulation of these pathways, and abovementioned pro-cancer and pro-death roles of mitophagy. Finally, we summarise the role of mitophagy in cancer therapy. Mitophagy can potentially be acted as the target for cancer therapy by promotion or inhibition. [ABSTRACT FROM AUTHOR]

In the study, the impact of protonectin (IL-12) on the bioavailability of human lung carcinoma cell line A549 as well as on HFLF healthy lung fibroblast cells was investigated for 24 h and 48 h. Results demonstrated highest cytotoxicity of protonectin on the A549 cell line at 12 µg/ml and 50 µg/ml, and after 48 h and 24 h cell incubation respectively. No cytotoxicity was observed during the incubation of normal HFLF lung cells with the IL-12 peptide. The peptide did not have any significant impact on the hemolysis of human and cattle red blood cells as well as on the viability of human lymphocytes. The effect of protonectin on gene expression of BMI-1 and CD44 as cancer markers was investigated by the real-time RT-PCR. Results indicated that the effect of the peptide on down-regulation of the BMI-1 gene expression was higher compared to CD44 at 12 µg/ml over 24 h and 48 h. A dose and time-dependent pattern was observed in the production of reactive oxygen species (ROS) in the treated A549 cells. From this study, it can be concluded that protonectin has a significant impact on cancer cells for the down-regulation of gene expression of cancer markers and for the up-regulation of the production of ROS. [ABSTRACT FROM AUTHOR]

One of the most notoriously altered genes in human cancer is the tumor-suppressor TP53 , which is mutated with high frequency in more cancers than any other tumor suppressor gene. Beyond the loss of wild-type p53 functions, mutations in the TP53 gene often lead to the expression of full-length proteins with new malignant properties. Among the defined oncogenic functions of mutant p53 is its effect on cell metabolism and autophagy. Due to the importance of autophagy as a stress adaptive response, it is frequently dysfunctional in human cancers. However, the role of p53 is enigmatic in autophagy regulation. While the complex action of the wild-type p53 on autophagy has extensively been described in literature, in this review, we focus on the conceivable role of distinct mutant p53 proteins in regulating different autophagic pathways and further discuss the available evidence suggesting a possible autophagy stimulatory role of mutant p53. Moreover, we describe the involvement of different autophagic pathways in targeting and degrading mutant p53 proteins, exploring the potential strategies of targeting mutant p53 in cancer by autophagy. [ABSTRACT FROM AUTHOR]

Non-small cell lung cancer (NSCLC), which represents 80–85% of lung cancer cases, is one of the leading causes of human death worldwide. The majority of patients undergo an intensive and invasive treatment regimen, which may include radiotherapy, chemotherapy, targeted therapy, immunotherapy, or a combination of these, depending on disease stage and performance status. Despite advances in therapeutic regimens, the 5-year survival of NSCLC is approximately 20–30%, largely due to diagnosis at advanced stages. Conventional chemotherapy is still the standard treatment option for patients with NSCLC, especially those with advanced disease. However, the emergence of resistance to chemotherapeutic agents (chemoresistance) poses a significant obstacle to the management of patients with NSCLC. Therefore, to develop efficacious chemotherapeutic approaches for NSCLC, it is necessary to understand the mechanisms underlying chemoresistance. Several mechanisms are known to mediate chemoresistance. These include altered cellular targets for chemotherapy, decreased cellular drug concentrations, blockade of chemotherapy-induced cell cycle arrest and apoptosis, acquisition of epithelial–mesenchymal transition and cancer stem cell-like phenotypes, deregulated expression of microRNAs, epigenetic modulation, and the interaction with tumor microenvironments. In this review, we summarize the mechanisms underlying chemoresistance and tumor recurrence in NSCLC and discuss potential strategies to avoid or overcome chemoresistance. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of antimalarials on cancer risk in patients with systemic lupus erythematosus (SLE). Methods: PubMed, EMBASE, Web of Science, and the Cochrane Library were searched from their inception to October 3, 2020. Relative risk (RR) with 95% confidence intervals (CI) was used to evaluate the results. Subgroup analyses were used to assess heterogeneity. A funnel plot was used to explore publication bias. STATA was applied for all analyses. Results: A total of nine studies consisted of four nested case-control, two case-cohort and three cohort studies were included. The results showed that antimalarials might reduce the risk of cancer in SLE (RR = 0.68, 95%CI: 0.55-0.85). In the subgroup analysis of four nested case-control and two case-cohort studies, the pooled RR was estimated as 0.69 (95% CI: 0.60-0.80). In four studies about hydroxychloroquine, the pooled RR was estimated as 0.70 (95% CI: 0.53-0.93). Antimalarials might reduce the risk of cancer in SLE among the Asian population (RR = 0.66; 95% CI: 0.49-0.88) (I2 = 43.1%, p<.173). And the consistent result was also found in SLE from multiple centres (RR = 0.72; 95%CI: 0.60-0.87) (I2 = 0%, p<.671). On disease courseand comorbidities-matched studies, the pooled RRs were 0.69 (95% CI: 0.52-0.93) and 0.59 (95% CI: 0.46-0.75), respectively. Conclusion: Results of this meta-analysis showed that antimalarial drugs might be protective factors for cancer in SLE. Hydroxychloroquine might be a protective factor for cancer in SLE patients. [ABSTRACT FROM AUTHOR]

Ovarian cancer (OC) is characterized by a high mortality rate due to the late diagnosis and the elevated metastatic potential. Autophagy, a lysosomal-driven catabolic process, contributes to the macromolecular turnover, cell homeostasis, and survival, and as such, it represents a pathway targetable for anti-cancer therapies. It is now recognized that the vascularization and the cellular composition of the tumor microenvironment influence the development and progression of OC by controlling the availability of nutrients, oxygen, growth factors, and inflammatory and immune-regulatory soluble factors that ultimately impinge on autophagy regulation in cancer cells. An increasing body of evidence indicates that OC carcinogenesis is associated, at least in the early stages, to insufficient autophagy. On the other hand, when the tumor is already established, autophagy activation provides a survival advantage to the cancer cells that face metabolic stress and protects from the macromolecules and organelles damages induced by chemo- and radiotherapy. Additionally, upregulation of autophagy may lead cancer cells to a non-proliferative dormant state that protects the cells from toxic injuries while preserving their stem-like properties. Further to complicate the picture, autophagy is deregulated also in stromal cells. Thus, changes in the tumor microenvironment reflect on the metabolic crosstalk between cancer and stromal cells impacting on their autophagy levels and, consequently, on cancer progression. Here, we present a brief overview of the role of autophagy in OC hallmarks, including tumor dormancy, chemoresistance, metastasis, and cell metabolism, with an emphasis on the bidirectional metabolic crosstalk between cancer cells and stromal cells in shaping the OC microenvironment. [ABSTRACT FROM AUTHOR]

Chemoresistance is a complex phenomenon responsible for failure in response to chemotherapy agents and more than 90% of deaths in cancer patients. MicroRNAs (miRNAs), as a subgroup of non-coding RNAs with lengths between 21 and 25 nucleotides, are involved in various cancer processes like chemoresistance via interacting with their target mRNAs and suppressing their expression. Autophagy is a greatly conserved procedure involving the lysosomal degradation of cytoplasmic contents and organelles to deal with environmental stresses like hypoxia and starvation. Autophagy contributes to response to chemotherapy agents: autophagy can act as a protective mechanism for mediating the resistance in response to chemotherapy or can induce autophagic cell death and mediate the sensitivity to chemotherapy. On the other hand, one of the processes targeted by microRNAs in the regulation of chemoresistance is autophagy. Hence, we studied the literatures on chemoresistance mechanisms, the miRNAs' role in cancer, and the miRNAs' role in chemoresistance by modulating autophagy. [ABSTRACT FROM AUTHOR]

Despite advances in cancer therapeutics and the integration of personalized medicine, the development of chemoresistance in many patients remains a significant contributing factor to cancer mortality. Upon treatment with chemotherapeutics, the disruption of homeostasis in cancer cells triggers the adaptive response which has emerged as a key resistance mechanism. In this review, we summarize the mechanistic studies investigating the three major components of the adaptive response, autophagy, endoplasmic reticulum (ER) stress signaling, and senescence, in response to cancer chemotherapy. We will discuss the development of potential cancer therapeutic strategies in the context of these adaptive resistance mechanisms, with the goal of stimulating research that may facilitate the development of effective cancer therapy. [ABSTRACT FROM AUTHOR]

Autophagy is a highly conserved intracellular degradation process that plays a crucial role in cell survival and stress reactions as well as in cancer development and metastasis. Autophagy process involves several steps including sequestration, fusion of autophagosomes with lysosomes and degradation. Forkhead box O (FOXO) transcription factors regulate the expression of genes involved in cellular metabolic activity and signaling pathways of cancer growth and metastasis. Recent evidence suggests that FOXO proteins are also involved in autophagy regulation. The relationship among FOXOs, autophagy, and cancer has been drawing attention of many who work in the field. This study summarizes the role of FOXO proteins and autophagy in cancer growth and metastasis and analyzes their potential roles in cancer disease management. [ABSTRACT FROM AUTHOR]

Cancer remains one of the leading causes of death worldwide, despite significant advances in cancer research and improvements in anticancer therapies. One of the major obstacles to curing cancer is the difficulty of achieving the complete annihilation of resistant cancer cells. The resistance of cancer cells may not only be due to intrinsic factors or factors acquired during the evolution of the tumor but may also be caused by chemotherapeutic treatment failure. Conversely, autophagy is a conserved cellular process in which intracellular components, such as damaged organelles, aggregated or misfolded proteins and macromolecules, are degraded or recycled to maintain cellular homeostasis. Importantly, autophagy is an essential mechanism that plays a key role in tumor initiation and progression. Depending on the cellular context and microenvironmental conditions, autophagy acts as a double-edged sword, playing a role in inducing apoptosis or promoting cell survival. In this review, we propose several scenarios in which autophagy could contribute to cell survival or cell death. Moreover, a special focus on novel promising targets and therapeutic strategies based on autophagic resistant cells is presented. [ABSTRACT FROM AUTHOR]

During tumorigenesis, cancer cells are exposed to a wide variety of intrinsic and extrinsic stresses that challenge homeostasis and growth. Cancer cells display activation of distinct mechanisms for adaptation and growth even in the presence of stress. Autophagy is a catabolic mechanism that aides in the degradation of damaged intracellular material and metabolite recycling. This activity helps meet metabolic needs during nutrient deprivation, genotoxic stress, growth factor withdrawal and hypoxia. However, autophagy plays a paradoxical role in tumorigenesis, depending on the stage of tumor development. Early in tumorigenesis, autophagy is a tumor suppressor via degradation of potentially oncogenic molecules. However, in advanced stages, autophagy promotes the survival of tumor cells by ameliorating stress in the microenvironment. These roles of autophagy are intricate due to their interconnection with other distinct cellular pathways. In this review, we present a broad view of the participation of autophagy in distinct phases of tumor development. Moreover, autophagy participation in important cellular processes such as cell death, metabolic reprogramming, metastasis, immune evasion and treatment resistance that all contribute to tumor development, is reviewed. Finally, the contribution of the hypoxic and nutrient deficient tumor microenvironment in regulation of autophagy and these hallmarks for the development of more aggressive tumors is discussed. [ABSTRACT FROM AUTHOR]

Cancer is one of most the significant threats to human health worldwide, and the primary method of treating solid tumours is surgery. Propofol, one of the most widely used intravenous anaesthetics in surgery, was found to be involved in many cancer‐related pathophysiology processes, mainly including anti‐tumour and minor cancer‐promoting effects in various types of cancer. An increasing number of studies have identified that propofol plays a role in cancer by regulating the expression of multiple signalling pathways, downstream molecules, microRNAs and long non‐coding RNAs. Emerging evidence has indicated that propofol can enhance the anti‐tumour effect of chemotherapeutic drugs or some small molecular compounds. Additionally, in vivo animal models have shown that propofol inhibits tumour growth and metastasis. Furthermore, most clinical trials indicate that propofol is associated with better survival outcomes in cancer patients after surgery. Propofol use is encouraged in cancers that appear to have a better prognosis after its use during surgery. We hope that future large and prospective multicenter studies will provide more precise answers to guide the choice of anaesthetics during cancer surgery. [ABSTRACT FROM AUTHOR]

Transcription factor 21 (TCF21) is a member of the basic helix-loop-helix (bHLH) transcription factors that mediate cell fate and differentiation by orchestrating temporal and spatial gene expression during the development of various organs. It plays a crucial role in a wide spectrum of biological processes, including organogenesis, epithelial-mesenchymal transition (EMT), cell cycle, autophagy, proliferation, differentiation, specification, maturation, and survival of cells, as well as invasion and metastasis of cancer cells. Controlled expression and activity of TCF21 provide a balanced transcriptional program that guarantees appropriate growth and maturation during embryogenesis and organ development. Its dysregulation is closely correlated with a variety of diseases, including cancer. Its function is mainly regulated by non-coding RNAs (ncRNAs), post-translational modifications (PTMs), and protein–protein interactions. However, the exact mechanisms of TCF21 dysregulation in disease progression are still elusive. This review summarizes the regulatory mechanisms of TCF21 expression and activity and highlights its critical role in health and disease. This information may contribute to the development of better diagnostics and treatments for cancer and other developmental diseases. [ABSTRACT FROM AUTHOR]

Introduction: Abnormalities in glucose metabolism in diabetic patients may lead to an increased risk of certain cancers. Epidemiological studies and meta-analysis have shown that factors such as gender, age, obesity, and insulin resistance are related to cancer incidence. The anti-p53 antibody is a known cancer marker due to tumor-associated p53 accumulation. Many studies have aimed to unravel the link between diabetes and cancer. Here, we aimed to elucidate the impact of diabetes on malignancies by analyzing anti-p53 antibody in sera of type 2 diabetes mellitus (T2DM) patients. Materials and Methods: We conducted an observational study with a cross-sectional design. A total of 149 subjects comprised of 78 T2DM patients (32 with cancer risk and 46 subjects without cancer risk), 51 T2DM patients with cancer, and 20 healthy subjects as controls from multisites. The anti-p53 antibody was measured by enzyme-linked immunosorbent assay, while HbA1c was measured using the NGSP standardized method. Results: We observed an 8.3-fold (p< 0.05) increase of anti-p53 antibody in the sera of T2DM patients and a 24-fold increase (p< 0.001) in T2DM patients with cancer compared to healthy subjects. The anti-p53 antibodies significantly increased almost three times (p< 0.05) in T2DM patients with cancer (0.72 U/mL± 0.20) compared to T2DM patients (0.25 U/mL± 0.05). Meanwhile, this antibody was almost undetectable in healthy subjects as a control group (0.03 U/mL± 0.03). The anti-p53 antibody level was higher in T2DM with cancer risk patients. However, we did not find a significant difference for it in T2DM without cancer risk patients (0.19 U/mL± 0.03) and T2DM with cancer risk patients (0.29 U/mL± 0.08). Multivariate regression analysis showed that T2DM with cancer was the only one independent factor (beta=0.218, p=0.019) that could predict the increase of anti-p53 antibody, controlled by age, gender, BMI, DM duration, and HbA1c. Conclusion: Our results showed that anti-p53 antibody almost not detected in healthy subjects, but 8.3-fold increase in the sera of T2DM patients and 24-fold increase in T2DM patients with cancer. Therefore, this biomarker provides new information which explains the link between diabetes and cancer. [ABSTRACT FROM AUTHOR]

Autophagy, as a type II programmed cell death, plays crucial roles with autophagy-related (ATG) proteins in cancer. Up to now, the dual role of autophagy both in cancer progression and inhibition remains controversial, in which the numerous ATG proteins and their core complexes including ULK1/2 kinase core complex, autophagy-specific class III PI3K complex, ATG9A trafficking system, ATG12 and LC3 ubiquitin-like conjugation systems, give multiple activities of autophagy pathway and are involved in autophagy initiation, nucleation, elongation, maturation, fusion and degradation. Autophagy plays a dynamic tumor-suppressive or tumor-promoting role in different contexts and stages of cancer development. In the early tumorigenesis, autophagy, as a survival pathway and quality-control mechanism, prevents tumor initiation and suppresses cancer progression. Once the tumors progress to late stage and are established and subjected to the environmental stresses, autophagy, as a dynamic degradation and recycling system, contributes to the survival and growth of the established tumors and promotes aggressiveness of the cancers by facilitating metastasis. This indicates that regulation of autophagy can be used as effective interventional strategies for cancer therapy. [ABSTRACT FROM AUTHOR]

Autophagy is an important cellular degradation pathway with a central role in metabolism as well as basic quality control, two processes inextricably linked to ageing. A decrease in autophagy is associated with increasing age, yet it is unknown if this is causal in the ageing process, and whether autophagy restoration can counteract these ageing effects. Here we demonstrate that systemic autophagy inhibition induces the premature acquisition of age-associated phenotypes and pathologies in mammals. Remarkably, autophagy restoration provides a near complete recovery of morbidity and a significant extension of lifespan; however, at the molecular level this rescue appears incomplete. Importantly autophagy-restored mice still succumb earlier due to an increase in spontaneous tumour formation. Thus, our data suggest that chronic autophagy inhibition confers an irreversible increase in cancer risk and uncovers a biphasic role of autophagy in cancer development being both tumour suppressive and oncogenic, sequentially. Autophagy declines with age, yet it is unclear if restoration of autophagy extends lifespan. Here, the authors demonstrate in murine models that the inhibition of Atg5 induces ageing phenotypes and reduces lifespan, whilst autophagy restoration partially reverses these phenotypes with accelerated tumorigenesis. [ABSTRACT FROM AUTHOR]

Purpose: Autophagy plays a vital role in cancer initiation, malignant progression, and resistance to treatment; however, autophagy-related gene sets have rarely been analyzed in glioblastoma. The purpose of this study was to evaluate the prognostic significance of autophagy-related genes in patients with glioblastoma. Patients and methods: Here, we collected whole transcriptome expression data from the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) datasets to explore the relationship between autophagy-related gene expression and glioblastoma prognosis. R language was the primary analysis and drawing tool. Results: We screened 531 autophagy-related genes and identified 14 associated with overall survival in data from 986 patients with glioblastoma. Patients could be clustered into two groups (high and low risk) using expression data from the 14 associated genes, based on significant differences in clinicopathology and prognosis. Next, we constructed a signature based on the 14 genes and found that most patients designated high risk using our gene signature were IDH wild-type, MGMT promoter non-methylated, and likely to have more malignant tumor subtypes (including classical and mesenchymal subtypes). Survival analysis indicated that patients in the high-risk group had dramatically shorter overall survival compared with their low-risk counterparts. Cox regression analysis further confirmed the independent prognostic value of our 14 gene signature. Moreover, functional and ESTIMATE analyses revealed enrichment of immune and inflammatory responses in the high-risk group. Conclusion: In this study, we identified a novel autophagy-related signature for the prediction of prognosis in patients with glioblastoma. [ABSTRACT FROM AUTHOR]

Continuous proliferation of tumor cells requires constant adaptations of energy metabolism to rapidly fuel cell growth and division. This energetic adaptation often comprises deregulated glucose uptake and lactate production in the presence of oxygen, a process known as the "Warburg effect." For many years it was thought that the Warburg effect was a result of mitochondrial damage, however, unlike this proposal tumor cell mitochondria maintain their functionality, and is essential for integrating a variety of signals and adapting the metabolic activity of the tumor cell. The mammalian/mechanistic target of rapamycin complex 1 (mTORC1) is a master regulator of numerous cellular processes implicated in proliferation, metabolism, and cell growth. mTORC1 controls cellular metabolism mainly by regulating the translation and transcription of metabolic genes, such as peroxisome proliferator activated receptor γ coactivator-1 α (PGC-1α), sterol regulatory element-binding protein 1/2 (SREBP1/2), and hypoxia inducible factor-1 α (HIF-1α). Interestingly it has been shown that mTORC1 regulates mitochondrial metabolism, thus representing an important regulator in mitochondrial function. Here we present an overview on the role of mTORC1 in the regulation of mitochondrial functions in cancer, considering new evidences showing that mTORC1 regulates the translation of nucleus-encoded mitochondrial mRNAs that result in an increased ATP mitochondrial production. Moreover, we discuss the relationship between mTORC1 and glutaminolysis, as well as mitochondrial metabolites. In addition, mitochondrial fission processes regulated by mTORC1 and its impact on cancer are discussed. Finally, we also review the therapeutic efficacy of mTORC1 inhibitors in cancer treatments, considering its use in combination with other drugs, with particular focus on cellular metabolism inhibitors, that could help improve their anti neoplastic effect and eliminate cancer cells in patients. [ABSTRACT FROM AUTHOR]