Blockage of Autophagy for Cancer Therapy: A Comprehensive Review.

Abstract

The incidence and mortality of cancer are increasing, making it a leading cause of death worldwide. Conventional treatments such as surgery, radiotherapy, and chemotherapy face significant limitations due to therapeutic resistance. Autophagy, a cellular self-degradation mechanism, plays a crucial role in cancer development, drug resistance, and treatment. This review investigates the potential of autophagy inhibition as a therapeutic strategy for cancer. A systematic search was conducted on Embase, PubMed, and Google Scholar databases from 1967 to 2024 to identify studies on autophagy inhibitors and their mechanisms in cancer therapy. The review includes original articles utilizing in vitro and in vivo experimental methods, literature reviews, and clinical trials. Key terms used were "Autophagy", "Inhibitors", "Molecular mechanism", "Cancer therapy", and "Clinical trials". Autophagy inhibitors such as chloroquine (CQ) and hydroxychloroquine (HCQ) have shown promise in preclinical studies by inhibiting lysosomal acidification and preventing autophagosome degradation. Other inhibitors like wortmannin and SAR405 target specific components of the autophagy pathway. Combining these inhibitors with chemotherapy has demonstrated enhanced efficacy, making cancer cells more susceptible to cytotoxic agents. Clinical trials involving CQ and HCQ have shown encouraging results, although further investigation is needed to optimize their use in cancer therapy. Autophagy exhibits a dual role in cancer, functioning as both a survival mechanism and a cell death pathway. Targeting autophagy presents a viable strategy for cancer therapy, particularly when integrated with existing treatments. However, the complexity of autophagy regulation and the potential side effects necessitate further research to develop precise and context-specific therapeutic approaches.