Targeting Autophagy in Cancer: Recent Advances and Future Directions
Year: 2019
Type: review
Abstract: Autophagy, a multistep lysosomal degradation pathway that supports nutrient recycling and metabolic adaptation, has been implicated as a process that regulates cancer. Although autophagy induction may limit the development of tumors, evidence in mouse models demonstrates that autophagy inhibition can limit the growth of established tumors and improve response to cancer therapeutics. Certain cancer genotypes may be especially prone to autophagy inhibition. Different strategies for autophagy modulation may be needed depending on the cancer context. Here, we review new advances in the molecular control of autophagy, the role of selective autophagy in cancer, and the role of autophagy within the tumor microenvironment and tumor immunity. We also highlight clinical efforts to repurpose lysosomal inhibitors, such as hydroxychloroquine, as anticancer agents that block autophagy, as well as the development of more potent and specific autophagy inhibitors for cancer treatment, and review future directions for autophagy research. SIGNIFICANCE: Autophagy plays a complex role in cancer, but autophagy inhibition may be an effective therapeutic strategy in advanced cancer. A deeper understanding of autophagy within the tumor microenvironment has enabled the development of novel inhibitors and clinical trial strategies. Challenges and opportunities remain to identify patients most likely to benefit from this approach.
Source: Cancer Discovery
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Stromal Fibroblast Autophagy In Tumor Progression and Desmoplasia, Targeted Therapies in Melanoma, G2955069778, Mechanisms of Selective Autophagy, G4722562889, Autophagy as a microenvironmental regulator of tumorigenesis and resistance, G518233734, G602611492, Investigating a novel glutamine metabolism pathway in pancreatic cancer, SPORE in Skin Cancer, Identifying Metabolic Dependencies of Pancreatic Cancers, Deciphering Autophagy-Dependent Secretion In Cancer Via Proximity-Based Biotinylation, Molecular mechanisms of BRAF inhibitor induced UPR and autophagy, Investigating the Role of Autophagy in Pancreatic Cancer Radiation Resistance, SPORE in Skin Cancer, Autophagy and Pro-metastatic Differentiation, Genetics and Biology of Pancreatic Ductal Adenocarcinoma, Cancer Center Support Grant, Abramson Cancer Center Support Grant
OpenAlex ID: W2969538494