in which we know another little bit about why the miracle cures never work

This paper looks nice. Like so much research it's not exactly "news" in the way that news outlets would like science stories to be.?? Research supporting what was already suspected. The most important specific example of a broader principle that was already known. One part in a pile of work that makes for a fascinating story, but of which no one piece was really news.

Drug resistance presents a challenge to the treatment of cancer patients. Many studies have focused on cell-autonomous mechanisms of drug resistance. By contrast, we proposed that the tumour micro-environment confers innate resistance to therapy. Here we developed a co-culture system to systematically assay the ability of 23 stromal cell types to influence the innate resistance of 45 cancer cell lines to 35 anticancer drugs. We found that stroma-mediated resistance is common, particularly to targeted agents. We characterized further the stroma-mediated resistance of BRAF-mutant melanoma to RAF inhibitors because most patients with this type of cancer show some degree of innate resistance. Proteomic analysis showed that stromal cell secretion of hepatocyte growth factor (HGF) resulted in activation of the HGF receptor MET, reactivation of the mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-OH kinase (PI(3)K)???AKT signalling pathways, and immediate resistance to RAF inhibition. Immunohistochemistry experiments confirmed stromal cell expression of HGF in patients with BRAF-mutant melanoma and showed a significant correlation between HGF expression by stromal cells and innate resistance to RAF inhibitor treatment. Dual inhibition of RAF and either HGF or MET resulted in reversal of drug resistance, suggesting RAF plus HGF or MET inhibitory combination therapy as a potential therapeutic strategy for BRAF-mutant melanoma. A similar resistance mechanism was uncovered in a subset of BRAF-mutant colorectal and glioblastoma cell lines. More generally, this study indicates that the systematic dissection of interactions between tumours and their micro-environment can uncover important mechanisms underlying drug resistance.

Ignore the specifics of the events it reports — lots of three-letter acronyms interacting with other three-letter acronyms. Three-letter acronyms are always interacting with other three-letter acronyms, and papers are always being published reporting a new set of interactions (or, more commonly, a dull variation on already well understood interactions). What they're saying is: the healthy tissues around tumours do funny things that affect how and even if drugs work, and knowing this will be useful when developing new drugs.

It's well established that different cells and tissues interact with each other in lots of different, only partly explored, ways. Including tumours, which we know, for example, exploit and manipulate healthy tissue for their metabolic needs. So it's not a big shock to learn this.

But the thing I find interesting is not so much what this means for future drug development, but the implications for all the past claims about cancer cures. I've written before about the limitations of tissue culture research, and the way they can be abused. Tumour cells which have been selected for their abnormal ability to grow spread out on a dish don't behave the same way as tumour cells in a tumour, in a body, protected under skin and fed by a circulatory system that connects it to a digestive system, liver, kidneys, and glands. And, it's increasingly clear, nestled up against healthy cells. It's why there's such a high failure rate in the translation from tissue culture research to real life. And it's why it's so easy for quacks and hacks to claim that the latest miracle cure or sinister hidden threat has been found…


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