Autophagy as a mechanism for anti-angiogenic therapy resistance. (November 2020)

• Record Type: Journal Article
• Authors: Chandra, Ankush; Rick, Jonathan; Yagnik, Garima; Aghi, Manish K.
• Is Part Of: Seminars in cancer biology. Volume 66(2021)
• Page Start: 75
• Page End: 88
• Publication Date: 2020-11
• Subjects: CAF cancer associated fibroblasts -- ECM extracellular matrix -- VEGF vascular endothelial growth factor -- HIF hypoxia-inducible factor -- PDGF platelet-derived growth factor -- GBM glioblastoma -- mRCC metastatic renal cell carcinoma -- TKI tyrosine kinase inhibitors -- VEGFR VEGF receptor -- TAN tumor associated neutrophils -- EPC endothelial progenitor cells -- FDA Food and Drug Administration -- CMA chaperone-mediated autophagy -- LAMP-2A lysosomal-associated membrane protein 2A (LAMP-2A) -- Atg autophagy-related proteins -- ER endoplasmic reticulum -- ULK1 Unc-51-like kinase 1 -- TFEB transcription factor EB -- AMBRA1 activating molecule in Beclin 1-regulated autophagy protein 1 -- GABARAP γ-aminobutyric acid receptor-associated proteins -- PI3P phosphatidylinositol-3-phosphate -- PE phosphatidylethanolamine -- LC3 Mmicrotubule-associated protein light chain 3 -- LIR LC3-interacting region -- SNAP synaptosomal-associated protein -- VAMP vesicle associated membrane protein -- STK serine/threonine-protein kinase -- ROS reactive oxygen species; Autophagy -- Angiogenesis -- Anti-angiogenesis -- Cancer -- VEGF -- Drug resistance; Cancer -- Periodicals; Neoplasms -- Periodicals; Review Literature; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.semcancer.2019.08.031
• Languages: English
• ISSNs: 1044-579X

Abstract

Abstract: Autophagy is a lysosomal-dependent degradation process that is highly conserved and maintains cellular homeostasis by sequestering cytosolic material for degradation either non-specifically by non-selective autophagy, or targeting specific proteins aggregates by selective autophagy. Autophagy serves as a protective mechanism defending the cell from stressors and also plays an important role in enabling tumor cells to overcome harsh conditions arising in their microenvironment during growth as well as oxidative and non-oxidative injuries secondary to therapeutic stressors. Recently, autophagy has been implicated to cause tumor resistance to anti-angiogenic therapy, joining an existing literature implicating autophagy in cancer resistance to conventional DNA damaging chemotherapy and ionizing radiation. In this review, we discuss the role of angiogenesis in malignancy, mechanisms of resistance to anti-angiogenic therapy in general, the role of autophagy in driving malignancy, and the current literature in autophagy-mediated anti-angiogenic therapy resistance. Finally, we provide future insight into the current challenges of using autophagy inhibitors in the clinic and provides tips for future studies to focus on to effectively target autophagy in overcoming resistance to anti-angiogenic therapy.