Vincent L. Cryns, MD

2007-2008 BCRF Project:
Made possible by generous support from The Housewares Charity Foundation
Co-Investigator: William J. Gradishar, MD FACP, Feinberg School of Medicine, Northwestern University

Recent studies have identified a new type of breast cancer, the basal-like tumors, which have a poor prognosis and account for 15-20% of all breast cancer cases and 39% of cases in young African-American women. However, the genes responsible for their aggressive behavior are unknown. Basal-like tumors are clinically aggressive and lack targeted therapies because they are estrogen receptor (ER)-negative and HER2-negative. Dr. Cryns and his colleagues have shown that turning off or "silencing" a cell stress protein called αB-crystallin in human basal-like breast cancer cells makes them more sensitive to chemotherapy drugs.

The Northwestern team has also examined the expression of αB-crystallin in breast tumors from women undergoing chemotherapy before surgery and found that breast tumors which expressed αB-crystallin responded poorly to chemotherapy compared to tumors which did not express this protein. These findings highlight the importance of developing new treatments for poor prognosis basal-like breast tumors, and they suggest that αB-crystallin may be a new drug target for these tumors.

In the coming year, Drs. Cryns and Gradishar will study the effects of turning off αB-crystallin on the ability of basal-like tumors to metastasize and to respond to chemotherapy in laboratory models. Their team will also screen large repositories or libraries of chemicals to identify drugs which make basal-like breast cancer cells expressing αB-crystallin more sensitive to chemotherapy. These studies will likely provide novel insights into the cause of basal-like breast cancer and may identify new drug candidates to treat these poor prognosis tumors.

Mid-Year Progress Report:
During the first few months of his current BCRF project, Drs. Cryns and Gradishar and colleagues have developed new laboratory models of basal-like breast cancer using fluorescently labeled breast cancer cells that can be visualized. Using this model, the Northwestern team is now examining whether silencing áB-crystallin blocks the growth and metastasis of basal-like tumors and makes them more susceptible to chemotherapy drugs. These studies will likely provide new molecular insights into the aggressive behavior of basal-like breast cancer and may lead to new treatment strategies.

Bio:
Dr. Cryns received his bachelor's degree Summa cum laude in biochemistry from Harvard, his M.D. from Harvard Medical School, and he did specialty training in endocrinology at Massachusetts General Hospital. His laboratory focuses on mechanisms of cell death. His lab was the first to report that a protein called αB-crystallin protects breast cancer cells from chemotherapy killing and elucidated the mechanism of this protection. Recently, Dr. Cryns' lab demonstrated that αB-crystallin plays an important role in an aggressive type of breast cancer (basal-like tumors) and predicts poor clinical outcomes. His research has been published in top medical journals, including the New England Journal of Medicine and the Journal of Clinical Investigation. His work has also been featured on National Public Radio's "All Things Considered" and highlighted in Nature and Nature Reviews Cancer.

Dr. Cryns' research is funded by the NIH, The Breast Cancer Research Foundation, the Susan G. Komen Breast Cancer Foundation and other agencies. He has also served on numerous study sections at NIH and other agencies. Dr. Cryns is currently on the editorial board of Molecular Endocrinology. He has been the recipient of several awards, including an Outstanding Junior Faculty Award from the Avon Foundation, and he is an elected member of the American Society for Clinical Investigation.