Annual Report 2013

DR. PETER NELSON IN HIS LAB FROM THE HUMAN BIOLOGY DIVISION

DR. PETER NELSON IN HIS LAB FROM THE HUMAN BIOLOGY DIVISION. Photo by Dean Forbes

Hutch leads charge that uncovers chemo resistance

Resistance to chemotherapy is almost as frustrating for oncologists as it is heartbreaking for cancer patients.

Thanks to a breakthrough by a team of scientists led by Fred Hutchinson Cancer Research Center, science is a significant step closer to understanding why chemotherapy fails to wipe out all of the tumor cells it targets.

The multi-center collaborative study, led by principal investigator Dr. Peter Nelson, determined that a normal, healthy cell found in connective tissue surrounding the tumor cells, the fibroblast, sustains DNA damage when exposed to chemotherapy. As a result of that damage, fibroblasts crank out a protein called WNT16B, which actually enables cancer growth and resistance to therapy.

Nelson and colleagues analyzed tissue samples from patients who underwent chemotherapy for prostate, breast or ovarian cancer. Their findings underscore the complexity of the microenvironment, or "neighborhood" in which cancer cells live and how changes in that environment impact cancer growth. Their findings also suggest that identifying a way to block fibroblast response to chemotherapy may improve treatment effectiveness.

"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," Nelson said. "Our findings indicate that the tumor microenvironment also can influence the success or failure of these more precise therapies."

The collaboration of scientists included researchers from the University of Washington, Oregon Health & Sciences University, the Novato, Calif.-based Buck Institute for Research on Aging and the Lawrence Berkeley National Laboratory in Washington, D.C.

"This study is an example of collaborative, translational research that capitalizes on years of federally funded investments into the development of tissue banks and clinical trials in which we were able to track long-term patient outcomes. Investing in this type of infrastructure is critical but may take many years to see payoff," Nelson said.

Dr. Peter Nelson's research is made possible in part through support provided by David & Doreen Keyes Foundation, the Canary Foundation and the Prostate Cancer Foundation.