Abstract
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.
Original language | English |
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Pages (from-to) | 2118-2129 |
Number of pages | 12 |
Journal | Cancer |
Volume | 123 |
DOIs | |
Publication status | Published - 1 Jun 2017 |
Keywords
- BRAF inhibitors
- immunotherapy
- melanoma
- mitogen-activated protein kinase (MAPK) pathway
- mitogen-activated protein kinase kinase (MEK) inhibitors
- phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway
- targeted therapy