Study finds new mechanism behind chemo resistance

A team of scientists has discovered a key factor that drives chemotherapy resistance-information that ultimately may be used to improve the effectiveness of therapy for cancer patients with solid tumors, including prostate cancer patients.

"Cancer cells inside the body live in a very complex environment or neighborhood. Where the tumor cell resides and who its neighbors are influence its response and resistance to therapy," said senior author Peter S. Nelson, MD, of Fred Hutchinson Cancer Center, Seattle.

Dr. Nelson and colleagues found that a fibroblast, when exposed to chemotherapy, sustains DNA damage that drives the production of a broad spectrum of growth factors that stimulate cancer growth. Specifically, the authors found that DNA-damaging cancer treatment coaxes fibroblasts to secrete a protein called WNT16B within the microenvironment and that high levels of this protein enable cancer cells to grow, invade surrounding tissue, and resist chemotherapy.

The authors observed up to 30-fold increases in WNT production, a finding that was "completely unexpected," Dr. Nelson said. This discovery suggests that finding a way to block this treatment response in the tumor microenvironment may improve the effectiveness of therapy.

"Cancer therapies are increasingly evolving to be very specific, targeting key molecular engines that drive the cancer rather than more generic vulnerabilities, such as damaging DNA. Our findings indicate that the tumor microenvironment also can influence the success or failure of these more precise therapies," he said.

The authors examined cancer cells from prostate, breast, and ovarian cancer patients who had been treated with chemotherapy.

Findings from the study were published online in Nature Medicine (Aug. 5, 2012).

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