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Making Tumor Cells More Vigorous Through. . .Chemotherapy?
Here’s some food for thought: in some cases, chemotherapy may actually accelerate the growth of tumor cells. This study has found that noncancerous cells (which are also affected, to various degrees, by most chemotherapy agents) can secrete Wnt16B in response to treatment, and that this protein is taken up by nearby tumor cells.
And that’s not good. Here’s the full paper, which looks at prostate cells. The secretion of the Wnt protein is mediated by NF-kappa-B in response to the DNA damage caused by many therapeutic agents, and it acts as a paracrine signal for the surrounding cells. And the resulting initiation of the Wnt pathway is bad news, because that’s already been implicated in tumor cell biology. Here’s the bad news slide: conditioned media from cultures of the normal prostate fibroblast cells, after exposure to therapeutic agents, causes prostate tumor cells to proliferate and become more mobile, an effect that can be canceled out by blocking Wnt16b.
Finding out that this can be set off by normal cells in the neighborhood means that we may need to do some rethinking about how chemotherapy is administered. But it would also seem to open a window to block Wnt signaling as an adjunct therapy. That’s already been the subject of a good amount of research, since the importance to tumor biology was already known – here’s a recent review. Development of these agents now looks more useful than ever. . .
Derek Lowe is a medicinal chemist with over 20 years experience in the drug industry. He blogs daily on science and drug discovery at In The Pipeline
2012-08-10 13:01:37
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