title: Emerging targets for combination therapy in melanomas.
abstract: Cutaneous melanomas are often difficult to treat when diagnosed in advanced stages. Melanoma cells adapt to survive in extreme environmental conditions and are among the tumors with larger genomic instability. Here we discuss some intrinsic and extrinsic mechanisms of resistance of melanoma cells to both conventional and target therapies, such as autophagy, adaptation to endoplasmic reticulum stress, metabolic reprogramming, mechanisms of tumor repopulation and the role of extracellular vesicles in this later phenomenon. These biological processes are potentially targetable and thus provide a platform for research and discovery of new drugs for combination therapy to manage melanoma patient treatment.
authors.affiliation: Center for Translational Research in Oncology (LIM24), Dept. of Radiology and Oncology, Faculdade de Medicina da Universidade de São Paulo and Instituto do Câncer do Estado de São Paulo, Brazil.
authors.forename: Renata de Freitas
authors.initials: Rde F
authors.lastname: Saito
authors.affiliation: Center for Translational Research in Oncology (LIM24), Dept. of Radiology and Oncology, Faculdade de Medicina da Universidade de São Paulo and Instituto do Câncer do Estado de São Paulo, Brazil.
authors.forename: Tharcísio Citrângulo
authors.initials: TC
authors.lastname: Tortelli
authors.affiliation: Center for Translational Research in Oncology (LIM24), Dept. of Radiology and Oncology, Faculdade de Medicina da Universidade de São Paulo and Instituto do Câncer do Estado de São Paulo, Brazil.
authors.forename: Mayara D'Auria
authors.initials: MD
authors.lastname: Jacomassi
authors.affiliation: Center for Translational Research in Oncology (LIM24), Dept. of Radiology and Oncology, Faculdade de Medicina da Universidade de São Paulo and Instituto do Câncer do Estado de São Paulo, Brazil.
authors.forename: Andréia Hanada
authors.initials: AH
authors.lastname: Otake
authors.affiliation: Center for Translational Research in Oncology (LIM24), Dept. of Radiology and Oncology, Faculdade de Medicina da Universidade de São Paulo and Instituto do Câncer do Estado de São Paulo, Brazil. Electronic address: rchammas@usp.br.
authors.forename: Roger
authors.initials: R
authors.lastname: Chammas
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use*; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D058990:Molecular Targeted Therapy / Q000379:methods*
keywords: Autophagy; Melanoma; Metabolic reprogramming; PAF; Tumor repopulation; Unfolded protein response