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Turning Bad Genes Good

May 10, 2018

Every year, about 22,440 American women learn they have ovarian cancer. And every year, about 14,000 women die from the disease.

Over the last two decades and aided by a grant from Women’s Health Research at Yale in 1999, Dr. Setsuko Chambers has directed a laboratory focused on understanding the molecular mechanisms underlying the development of ovarian and breast cancer.

“The level of sophistication of our recent work has advanced tremendously since 1999, both conceptually and in terms of the explosion in development of experimental methods,” Chambers said. “We have expanded on the basic work we were able to perform back then, as a result of WHRY’s pilot funding.”

When Chambers received her WHRY grant, she was an Associate Professor of Gynecologic Oncology, seeking a way to target genes within cancer cells that control aggressive tumor behavior to enhance patient survival and decrease toxicity from chemotherapy. Focusing on ribonucleic acid (RNA), a molecule that works with deoxyribonucleic acid (DNA) to carry out genetic instructions, Chambers’ work revealed more about how molecular processes behaved within an ovarian cancer cell, advancing the development of therapies used to treat this disease.

“Gene therapy utilizing RNAs as we proposed in 1999 was novel then but ahead of its time,” she said. “It turned out that RNA decoys — RNA created to mimic and redirect the function of naturally occurring RNA in a cancer cell — could not be realistically delivered to patients, although the mechanisms proposed were sound. Thanks in part to our findings, the field of ovarian cancer treatment evolved to embrace targeted therapies such as small molecule inhibitors and antibodies.”

These therapies led to huge progress, after decades of stagnation, in immunotherapy, which involves triggering the body’s disease-eliminating immune system to recognize cancer cells as foreign substances and kill them instead of accepting them as extensions of the body’s healthy processes.

Dr. Chambers was recruited from Yale to the University of Arizona Cancer Center in 2004 and has since been elected to the National Academy of Sciences Health and Medicine Division while serving as the center’s Director of Women’s Cancers and Vice Chair of the Department of Obstetrics and Gynecology. She has developed the center’s clinic for women at high risk for ovarian and breast cancer, focusing on how genetic testing might provide insight for risk assessment of subgroup populations for early detection as well as a way to gauge the response of tumors to specific therapies.

As one of the few gynecologic oncologist physician-scientists in the country, Chambers leads a team of interdisciplinary clinicians and researchers focused on delivering the best care to women grounded in the latest science. She expressed the need for programs like Women’s Health Research at Yale to continue supporting researchers so they might obtain the data necessary to advance our understanding of and ability to treat diseases and conditions that affect millions of people.

“When I began this work at Yale, pilot funding was critical as a basis to get preliminary data for larger grants,” she said. “And with today’s competition and shrinking pools of federal dollars, such pilot funding is even more important.”

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Submitted by Carissa R Violante on May 10, 2018

About the Investigator —

Dr. Setsuko Chambers earned her M.D. and B.S. at Brown University. She is currently a Professor of Obstetrics and Gynecology and of Medicine and of Cancer Biology at The University of Arizona Cancer Center, Vice Chair of the Department of Obstetrics and Gynecology, Director of Gynecologic Oncology, Director of Women’s Cancers, and the Bobbi Olson Endowed Chair in Ovarian Cancer Research.

Dr. Chambers is an elected member of the National Academy of Sciences Health and Medicine Division and developed The University of Arizona Cancer Center’s Division of Women’s Cancers to deploy genetic testing as a way to better detect and treat ovarian and breast cancer.