Scientists find new mechanism behind resistance to cancer treatment

By | August 5, 2012

Medical Xpress: “A team of scientists led by Fred Hutchinson Cancer Research Center has discovered a key factor that drives this drug resistance [chemotherapy resistance].Nelson and colleagues found that a type of normal, noncancerous cell that lives in cancer’s neighborhood – the 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 researchers found that DNA-damaging cancer treatment coaxes fibroblasts to crank out a protein called WNT16B within the tumor neighborhood, or microenvironment, and that high levels of this protein enable cancer cells to grow, invade surrounding tissue and resist chemotherapy.” – Interesting finding. I suppose that means we’ll be looking at WNT16B inhibitors soon? Probably not soon. A quick Google search revealed that that protein may contribute to several other processes in the human body.

Article from Nature Medicine below.

Treatment-induced damage to the tumor microenvironment promotes prostate cancer therapy resistance through WNT16B

Abstract
Acquired resistance to anticancer treatments is a substantial barrier to reducing the morbidity and mortality that is attributable to malignant tumors. Components of tissue microenvironments are recognized to profoundly influence cellular phenotypes, including susceptibilities to toxic insults. Using a genome-wide analysis of transcriptional responses to genotoxic stress induced by cancer therapeutics, we identified a spectrum of secreted proteins derived from the tumor microenvironment that includes the Wnt family member wingless-type MMTV integration site family member 16B (WNT16B). We determined that WNT16B expression is regulated by nuclear factor of κ light polypeptide gene enhancer in B cells 1 (NF-κB) after DNA damage and subsequently signals in a paracrine manner to activate the canonical Wnt program in tumor cells. The expression of WNT16B in the prostate tumor microenvironment attenuated the effects of cytotoxic chemotherapy in vivo, promoting tumor cell survival and disease progression. These results delineate a mechanism by which genotoxic therapies given in a cyclical manner can enhance subsequent treatment resistance through cell nonautonomous effects that are contributed by the tumor microenvironment.

(10.1038/nm.2890)

Just a quick observation, the article was submitted in April 2011. Yes, well over a year ago. Published online August 2012. I wonder where the research on this protein is today? About half the authors are from the Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington. I wonder if they’d mind if I dropped in next time I was in the area?

Bibliography

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