Targeting autophagy as a potential therapeutic approach for melanoma therapy

Abstract

Melanoma, occurring as a rapidly progressive skin cancer, is resistant to current chemo- and radiotherapy, especially after metastases to distant organs has taken place. Most chemotherapeutic drugs exert their cytotoxic effect by inducing apoptosis, which, however, is often deficient in cancer cells. Thus, it is appropriate to attempt the targeting of alternative pathways, which regulate cellular viability. Recent studies of autophagy, a well-conserved cellular catabolic process, promise to improve the therapeutic outcome in melanoma patients. Although a dual role for autophagy in cancer therapy has been reported, both protecting against and promoting cell death, the potential for using autophagy in cancer therapy seems to be promising. Here, we review the recent literature on the role of autophagy in melanoma with respect to the expression of autophagic markers, the involvement of autophagy in chemo- and immunotherapy, as well as the role of autophagy in hypoxia and altered metabolic pathways employed for melanoma therapy.

Keywords: 3-MA; 3-methyladenine; 5-ALA; 5-aminolevulinic acid; AMBRA1; APC; ASS; ATG; ATM; Ataxia telangiectasia mutated; Autophagy; BN; BafA1; Bif-1; CQ; CTL; CTLA-4; Cav-1; Chemotherapy; DDR; DN; DNA damage response; DRiPs; EM; ER; GA-DM; HIF; HLA; Hypoxia; IFN; Immunotherapy; LAMP2; LC3; MHC; Melanoma; PCL; PE; PEDF; PEI; PFS; PI3K; PI3P; RGP; ROS; SKP; TMA; TRAIL; ULK1; UV radiation resistance associated gene; UVRAG; VGP; antigen-presenting cell; argininosuccinate synthetase; autophagy-related; autophagy/Beclin 1 regulator 1; bafilomycin A1; benign nevi; caveolin-1; chloroquine; cytolytic T lymphocyte; cytotoxic T-lymphocyte antigen 4; defective ribosomal products; dysplastic nevi; electron microscopy; endophilin B1; endoplasmic reticulum; ganoderic acid-dextromethorphan; human leukocyte antigen; hypoxia-inducible factor; interferon; lysosomal-associated membrane protein 2; mTOR; major histocompatibility complex; mammalian target of rapamycin; microtubule-associated protein 1 light chain 3; phophatidylinositol-3-phosphate; phosphatidylethanolamine; phosphoinositide 3-kinase; pigment epithelium-derived factor receptor; polyethylene imine; polygonatum cyrtonema lectin; progression free survival; radial growth phase; reactive oxygen species; skin-derived precursor; tissue microarray; tumor necrosis factor-related apoptosis-inducing ligand; unc-51-like kinase 1; vertical growth phase.