Two independent research teams have used
cell culture methods to show that high hepatocyte growth factor/scatter factor levels drive resistance to BRAF
inhibitors in melanoma.1,2 The findings could provide a rationale
for combining hepatocyte growth factor/scatter factor or c-Met proto-oncogene inhibitors with BRAF inhibitors to overcome treatment
resistance in the disease.
Providing the relevance
"Both studies provide new
information that can be quickly applied in the clinic. The immediate next step
is to use stromal HGF/SF levels or tumor MET overexpression as potential
predictive biomarkers of response to combined BRAF inhibition plus HGF/MET
antagonists for clinical trials in BRAF mutant melanoma," said Roger Lo. "And
in the long run, the screening strategy will help to guide strategic selection
of combination therapies to treat a variety of cancers."
A different kind of animal
The findings of the two papers also will
change how researchers use animal studies to model in vivo relevance.
Baas, T. SciBX 5(32);
Published online Aug. 16, 2012
1. Wilson, T.R. et al. Nature; published online July 4, 2012;
Contact: Jeffrey Settleman, Genentech Inc., South San
2. Straussman, R. et al. Nature; published online July 4, 2012;
Contact: Todd R. Golub, Broad Institute of MIT and Harvard,
3. Harbinski, F. et al. Cancer
Discov.; published online Aug. 8,
Contact: Ralph Tiedt, Novartis Institutes for BioMedical
Research, Basel, Switzerland
Amgen Inc. (NASDAQ:AMGN), Thousand Oaks, Calif.
Aveo Pharmaceuticals Inc. (NASDAQ:AVEO), Cambridge, Mass.
Broad Institute of MIT and Harvard, Cambridge, Mass.
Chugai Pharmaceutical Co. Ltd. (Tokyo:4519), Tokyo, Japan
Daiichi Sankyo Co. Ltd. (Tokyo:4568; Osaka:4568), Tokyo, Japan
Dana-Farber Cancer Institute, Boston, Mass.
Genentech Inc., South San Francisco, Calif.
Harvard Medical School, Boston, Mass.
Novartis AG (NYSE:NVS; SIX:NOVN), Basel, Switzerland
Pfizer Inc. (NYSE:PFE), New York, N.Y.
(SIX:ROG; OTCQX:RHHBY), Basel, Switzerland
University of California, Los Angeles David Geffen School
of Medicine, Los