Targeted therapy resistance mechanisms and therapeutic implications in melanoma

Guo Chen; Michael A Davies

doi:10.1016/j.hoc.2014.03.001

Targeted therapy resistance mechanisms and therapeutic implications in melanoma

Hematol Oncol Clin North Am. 2014 Jun;28(3):523-36. doi: 10.1016/j.hoc.2014.03.001.

Authors

Guo Chen¹, Michael A Davies²

Affiliations

¹ Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 904, Houston, TX 77030, USA.
² Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 904, Houston, TX 77030, USA. Electronic address: mdavies@mdanderson.org.

PMID: 24880945
DOI: 10.1016/j.hoc.2014.03.001

Abstract

Although selective mutant BRAF inhibitors have revolutionized the treatment of metastatic melanoma, the magnitude and duration of their clinical benefit are significantly undermined by de novo and acquired resistance. Functional studies, molecular characterization of clinical samples, and clinical trials are providing insights into the landscape of resistance mechanisms in this disease. These findings have implications for the development of rational therapeutic approaches, and have identified several challenges that remain to be overcome if outcomes are to be improved in patients with metastatic melanoma.

Keywords: BRAF(V600); Combination therapy; Drug resistance; MAPK; Melanoma; PI3K/AKT; Tumor heterogeneity.

Publication types

Review

MeSH terms

Drug Resistance, Neoplasm / genetics
Humans
Melanoma / drug therapy*
Melanoma / genetics
Models, Genetic
Molecular Targeted Therapy / methods*
Mutation
Protein Kinase Inhibitors / therapeutic use
Proto-Oncogene Proteins B-raf / genetics
Signal Transduction / drug effects
Signal Transduction / genetics
Skin Neoplasms / drug therapy*
Skin Neoplasms / genetics

Substances

Protein Kinase Inhibitors
Proto-Oncogene Proteins B-raf