Komen Foundation grant enables TGen scientists to study triple-negative breast cancer

The Translational Genomics Research Institute (TGen) is part of a team of medical investigators receiving a $3.5 million grant from Susan G. Komen for the Cure to study triple-negative breast cancer, a highly aggressive form of this cancer that disproportionately affects African-Americans.

The Komen Foundation recently called for proposals from teams of physicians and scientists called Promise Grants, multi-million dollar, multi-year, collaborative grants aimed at answering the most difficult questions in breast cancer and translating their findings into outcomes that will impact patient care.

Only three teams were selected for funding for this highly competitive program. The team leaders for this proposal are: Dr. Jeffrey Trent of Phoenix-based TGen; Dr. Pat LoRusso of the Karmanos Cancer Institute in Detroit; and Dr. Max Wicha of The University of Michigan Comprehensive Cancer Center. Other centers collaborating on this project include the Van Andel Research Institute (VARI) in Grand Rapids, which is TGen's affiliate, and the Baylor College of Medicine in Houston.

The collective expertise of these oncologists and basic scientists will be brought to bear on this landmark translational research study. Three specific biomarkers that are used to determine breast cancer treatment are missing in triple-negative breast cancer. The most successful treatment advances in breast cancer have targeted these three markers. None of these therapies are effective in triple-negative breast cancer.

"We hope to uncover new ways of treating this very aggressive form of breast cancer by understanding the molecular makeup of breast cancer stem cells," said Dr. John Carpten, Director of TGen's Integrated Cancer Genomics Division, who is leading other translational investigations into triple-negative breast cancer and is a co-investigator on the new Komen study. "Our goal is to unlock the clues as to why patients with triple-negative breast cancer so often fail to respond to available therapies, and to design new ways to more effectively treat this difficult form of cancer."

Dr. Wicha, M.D., Distinguished Professor of Oncology and Director of the U-M Comprehensive Cancer Center, was one of the first to identify cancer "stem cells" in solid tumors, recognizing them in breast cancer tissue in 2003. Cancer stem cells are the small number of cells within a tumor that continually fuel the tumor's growth and spread, rendering the tumor resistent to today's therapies. Many researchers believe traditional chemotherapy and radiation treatments often become ineffective because they do not kill the cancer stem cells, and that the key to future treatments is to develop drugs that target and kill these cells. Research suggests that triple-negative breast cancers have a higher proportion of cancer stem cells.

Among women with breast cancer, triple negative breast cancer represents about 15 percent of diagnoses in Caucasian American women, but 26 percent in African American women and up to 82 percent in west African women. The grant proposal includes studying tumor cells from African and African-American women to look for molecular differences in triple-negative tumors. Laboratory research will look at whether targeting the breast cancer stem cells has an impact on these tumors.

"Through this research study, we will be able to provide key insights into whether or not cancer stem cells plays a role in the significant differences observed in death rates among women of west African origin who are more likely to be diagnosed with, and die from, this terrible form of cancer," said Dr. Heather Cunliffe, Head of TGen's Breast & Ovarian Cancer and a co-investigator on the study.

Researchers also plan to launch at least three clinical trials to investigate new treatments that target cancer stem cells. Based on the results of these trials, a larger randomized clinical trial will be planned.

"TGen scientists lead by Dr. John Carpten have been at the forefront of cancer health disparities research for more than a decade," said Dr. Trent, President and Research Director of TGen and VARI. "This study is at the vanguard of treatments that are aimed at the most deadly form of human breast cancer in a this highly vulnerable patient population."

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