{"title":"Navigating therapeutic prospects by modulating autophagy in colorectal cancer","authors":"","doi":"10.1016/j.lfs.2024.123121","DOIUrl":null,"url":null,"abstract":"<div><div>Colorectal cancer (CRC) remains a leading cause of death globally despite the improvements in cancer treatment. Autophagy is an evolutionarily conserved lysosomal-dependent degradation pathway that is critical in maintaining cellular homeostasis. However, in cancer, autophagy may have conflicting functions in preventing early tumour formation versus the maintenance of advanced-stage tumours. Defective autophagy has a broad and dynamic effect not just on cancer cells, but also on the tumour microenvironment which influences tumour progression and response to treatment. To add to the layer of complexity, somatic mutations in CRC including tumour protein p53 (TP53), v-raf murine sarcoma viral oncogene homolog B1 (BRAF), Kirsten rat sarcoma viral oncogene homolog (KRAS), and phosphatase and tensin homolog (PTEN) can render chemoresistance by promoting a pro-survival advantage through autophagy. Recent studies have also reported autophagy-related cell deaths that are distinct from classical autophagy by employing parts of the autophagic machinery, which impacts strategies for autophagy regulation in cancer therapy. This review discusses the molecular processes of autophagy in the evolution of CRC and its role in the tumour microenvironment, as well as prospective therapeutic methods based on autophagy suppression or promotion. It also highlights clinical trials using autophagy modulators for treating CRC, underscoring the importance of autophagy regulation in CRC therapy.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":null,"pages":null},"PeriodicalIF":5.2000,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Life sciences","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0024320524007112","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
Abstract
Colorectal cancer (CRC) remains a leading cause of death globally despite the improvements in cancer treatment. Autophagy is an evolutionarily conserved lysosomal-dependent degradation pathway that is critical in maintaining cellular homeostasis. However, in cancer, autophagy may have conflicting functions in preventing early tumour formation versus the maintenance of advanced-stage tumours. Defective autophagy has a broad and dynamic effect not just on cancer cells, but also on the tumour microenvironment which influences tumour progression and response to treatment. To add to the layer of complexity, somatic mutations in CRC including tumour protein p53 (TP53), v-raf murine sarcoma viral oncogene homolog B1 (BRAF), Kirsten rat sarcoma viral oncogene homolog (KRAS), and phosphatase and tensin homolog (PTEN) can render chemoresistance by promoting a pro-survival advantage through autophagy. Recent studies have also reported autophagy-related cell deaths that are distinct from classical autophagy by employing parts of the autophagic machinery, which impacts strategies for autophagy regulation in cancer therapy. This review discusses the molecular processes of autophagy in the evolution of CRC and its role in the tumour microenvironment, as well as prospective therapeutic methods based on autophagy suppression or promotion. It also highlights clinical trials using autophagy modulators for treating CRC, underscoring the importance of autophagy regulation in CRC therapy.
期刊介绍:
Life Sciences is an international journal publishing articles that emphasize the molecular, cellular, and functional basis of therapy. The journal emphasizes the understanding of mechanism that is relevant to all aspects of human disease and translation to patients. All articles are rigorously reviewed.
The Journal favors publication of full-length papers where modern scientific technologies are used to explain molecular, cellular and physiological mechanisms. Articles that merely report observations are rarely accepted. Recommendations from the Declaration of Helsinki or NIH guidelines for care and use of laboratory animals must be adhered to. Articles should be written at a level accessible to readers who are non-specialists in the topic of the article themselves, but who are interested in the research. The Journal welcomes reviews on topics of wide interest to investigators in the life sciences. We particularly encourage submission of brief, focused reviews containing high-quality artwork and require the use of mechanistic summary diagrams.