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Mechanisms and strategies to overcome resistance to molecularly targeted therapy for melanoma
Author(s) -
Lim Su Yin,
Menzies Alexander M.,
Rizos Helen
Publication year - 2017
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.30435
Subject(s) - medicine , melanoma , neuroblastoma ras viral oncogene homolog , pi3k/akt/mtor pathway , mapk/erk pathway , targeted therapy , protein kinase b , cancer research , cancer , protein kinase a , kinase , signal transduction , bioinformatics , oncology , biology , colorectal cancer , kras , genetics
The identification of driver mutations in melanoma has changed the field of cancer treatment. BRAF and NRAS mutations are predominant in melanoma and lead to overactivation of the mitogen‐activated protein kinase (MAPK) and phosphatidylinositol 3‐kinase (PI3K)/protein kinase B (AKT) signaling pathways. Selective inhibitors targeting key effectors of the MAPK pathway have revolutionized the treatment of patients with advanced metastatic BRAF‐mutant melanoma. However, resistance to therapy is almost universal and remains a major challenge in clinical care, with the majority of patients progressing within 1 year. Dissecting the mechanisms of resistance to targeted therapies may offer new insights into strategies for overcoming resistance. This review describes the efficacy of therapies targeting the MAPK and PI3K/AKT signaling pathways in melanoma, details the mechanisms contributing to drug resistance, and discusses current approaches to improving outcomes further. Cancer 2017;123:2118‐29. © 2017 American Cancer Society .