In a paper published online in advance in Nature this week, researchers at the Broad Institute and elsewhere report on a co-culture system they developed "to systematically assay the ability of 23 stromal cell types to influence the innate resistance of 45 cancer cell lines to 35 anticancer drugs." Finding stroma-mediate resistance common, the team went on to characterize one particular form — stroma-mediated resistance of BRAF-mutant melanoma to RAF inhibitors. Proteomic and immunohistochemical workups implicated hepatocyte growth factor in such resistance. Overall, the team observed a "significant correlation between HGF expression by stromal cells and innate resistance to RAF inhibitor treatment," as it writes in Nature.
"Even though recent advanced in targeted therapy have caused tremendous excitement in melanoma, the fact remains that drug resistance eventually develops in nearly all metastatic melanomas treated with RAF inhibitors, and in some cases is present at the outset of treatment," says the Broad's Levi Garraway in a statement. "There are many different types of mechanisms that tumors may hijack to circumvent the effects of therapy … no single experimental approach can capture all of these potential mechanisms. Thus, the application of complementary approaches can offer considerable synergy in terms of discovering the full spectrum of clinically relevant resistance mechanisms."