Tumor adaptation and resistance to RAF inhibitors Journal Article


Authors: Lito, P.; Rosen, N.; Solit, D. B.
Article Title: Tumor adaptation and resistance to RAF inhibitors
Abstract: RAF kinase inhibitors have substantial therapeutic effects in patients with BRAF-mutant melanoma. However, only rarely do tumors regress completely, and the therapeutic effects are often temporary. Several mechanisms of resistance to RAF inhibitors have been proposed. The majority of these cause ERK signaling to become insensitive to treatment with RAF inhibitors by increasing the amount of RAF dimers in cells, whereas others bypass the dependence of the tumor on mutant RAF. One motivation for studying mechanisms of drug resistance is that such efforts may suggest new therapeutic targets or rational combination strategies that delay or prevent the emergence of drug-resistant clones. Here, we review the current model of RAF inhibitor resistance with a focus on the implications of this model on ongoing laboratory and clinical efforts to develop more effective therapeutic strategies for patients with BRAF-mutant tumors. © 2013 Nature America, Inc.
Journal Title: Nature Medicine
Volume: 19
Issue: 11
ISSN: 1078-8956
Publisher: Nature Publishing Group  
Date Published: 2013-11-01
Start Page: 1401
End Page: 1409
Language: English
DOI: 10.1038/nm.3392
PROVIDER: scopus
PUBMED: 24202393
DOI/URL:
Notes: --- - "Export Date: 2 December 2013" - "CODEN: NAMEF" - "Source: Scopus"
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  1. Neal Rosen
    425 Rosen
  2. David Solit
    780 Solit
  3. Piro Lito
    58 Lito