Microenvironment-driven resistance to BRAF inhibition comes of age

Menon, Dinoop Ravindran and Schaider, Helmut (2015) Microenvironment-driven resistance to BRAF inhibition comes of age. Journal of Investigative Dermatology, 135 12: 2923-2925. doi:10.1038/jid.2015.373


Author Menon, Dinoop Ravindran
Schaider, Helmut
Title Microenvironment-driven resistance to BRAF inhibition comes of age
Journal name Journal of Investigative Dermatology   Check publisher's open access policy
ISSN 1523-1747
0022-202X
Publication date 2015-12-01
Year available 2015
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1038/jid.2015.373
Open Access Status Not yet assessed
Volume 135
Issue 12
Start page 2923
End page 2925
Total pages 3
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Formatted abstract
Increasingly comprehensive observations indicate that the tumor microenvironment contributes to drug resistance toward small molecule inhibitors. Fedorenko et al. describe a role for fibroblasts in creating a favorable niche for melanoma cell survival if treated with the BRAF inhibitor vemurafenib. TGF-β released by vemurafenib-treated melanoma cells stimulated fibroblasts for increased α-smooth muscle actin, neuregulin (NRG), and fibronectin expression. Off-target effects of vemurafenib led to paradoxical secretion of hepatocyte growth factor (HGF) by fibroblasts. Combined inhibition of BRAF/MET/HER kinases was insufficient to reverse the protective effect of the fibroblasts, whereas reversal was achieved by combined BRAF/PI3K inhibition. A thorough understanding of the complex spatiotemporal interactions in tumor microenvironments holds promise for improved targeting using combination therapies in patients with melanoma.
Q-Index Code CX
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: Non HERDC
School of Medicine Publications
UQ Diamantina Institute Publications
 
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