BRAF Inhibitors for the Treatment of Metastatic Melanoma: Clinical Trials and Mechanisms of Resistance

DOI PDF 2 Citations
  • Alexander Marzuka Alcalá
    Authors' Affiliations: 1Yale School of Medicine, New Haven, Connecticut; 2Massachusetts General Hospital Cancer Center, Boston, Massachusetts
  • Keith T. Flaherty
    Authors' Affiliations: 1Yale School of Medicine, New Haven, Connecticut; 2Massachusetts General Hospital Cancer Center, Boston, Massachusetts

Description

<jats:title>Abstract</jats:title> <jats:p>The efficacy of selective BRAF inhibitors has now been established in the 50% of patients with metastatic melanoma whose tumors harbor activating mutations. However, for the vast majority of patients, responses persist for less than a year. In extensive preclinical investigations, researchers have focused on potential resistance mechanisms with the hope of identifying treatment strategies that can overcome resistance. Preliminary results suggest that reactivation of the mitogen-activated protein kinase (MAPK) pathway by several BRAF-independent mechanisms is the predominant pattern. However, MAPK pathway–independent mechanisms also seem to play a potential role. More definitive cataloging of resistance mechanisms in patients' tumor samples is needed as combination regimens are being readied for clinical evaluation. Clin Cancer Res; 18(1); 33–9. ©2012 AACR.</jats:p>

Journal

  • Clinical Cancer Research

    Clinical Cancer Research 18 (1), 33-39, 2012-01-01

    American Association for Cancer Research (AACR)

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