Research targets aggressive, hard-to-treat breast cancer
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Cancer comes in a dizzying array of varieties. But one thing many breast cancers share is a tendency to activate a protein known as SIAH, a so-called “biomarker” readily detected in human cancers.
Research undertaken by Macon & Joan Brock Virginia Health Sciences at Old Dominion University scientists and Sentara Health clinicians already has proven SIAH to be a powerful tool for both diagnosing and treating cancer. Now, supported by a $2.5 million grant from the Department of Defense and joined by clinicians and scientists at Virginia Commonwealth University and George Mason University, this multicenter team has set its sights on a new challenge, one with life-saving implications for women — especially in Virginia.
The researchers are targeting triple-negative breast cancer (TNBC), a particularly aggressive, multi-drug resistant cancer that can quickly metastasize and spread, said Amy Tang, Ph.D., Professor of Biomedical and Translational Sciences in the Leroy T. Canoles Cancer Research Center at Macon & Joan Brock Virginia Health Sciences at Old Dominion University and the primary principal investigator.
Dr. Richard Hoefer
Triple-negative is the deadliest form of breast cancer. It is more common in women who are younger than age 40, who are Black or who have a gene mutation that makes them more susceptible. For unknown reasons, women from low-income communities in Virginia suffer from high rates of TNBC.
“Cancer occurs when cells subdivide uncontrollably, much like a runaway car,” Dr. Tang explains. “SIAH functions like the transmission of these runaway cells, helping to propel them down the road to becoming cancerous.”
“We have demonstrated how the presence or absence of SIAH — the function and disfunction of the transmission system of cancer cell communications — can help predict how patients will respond to cancer treatment,” Dr. Tang says. “Will their cancer be eliminated, stay in remission or will they relapse? This is important for selecting effective cancer treatment regimens.”
“In our new research, we aim to demonstrate and validate the prognostic accuracy and clinical utility of incorporating SIAH protein expression as a tumor-specific, therapy-responsive and quantitative new prognostic biomarker to risk stratify TNBC patients in a large, racially diverse population in central and eastern Virginia,” she says.
The researchers believe the level of SIAH tumor expresses is key, providing vital insight into the tumor’s behavior and helping to risk stratify patients, quantify therapy efficacy, and guide treatment decisions.
By targeting the transmission system in cancer cells, the team’s goal is to expand the existing cancer arsenal and armamentarium in hopes of controlling and eradicating high-grade and late-stage malignancy.
Dr. Harry Bear
“Our earlier TNBC research showcased the curative potential of a home-made potent SIAH inhibitor, SIAH(PD), that has eradicated multiple stage IV human cancer cell lines in mice,” Dr. Tang says. “During the new DOD-funded research, we will test the SIAH inhibitor’s curative capabilities in TNBC tumor models with broad genetic diversity and epigenetic heterogeneity.”
Dr. Tang highlighted the support of leadership from Sentara and Macon & Joan Brock Virginia Health Sciences at Old Dominion University along with Cindy Allen, B.S.N., and Richard Hoefer, D.O., at the Sentara Health Research Center for their role in helping secure research funding. Dr. Hoefer and Harry Bear, M.D., Ph.D., at VCU Massey Cancer Center in Richmond, will advise and lead the clinical aspects of the DOD-funded breakthrough research in TNBC.
The latest research also owes its beginnings in part to the Dorothy G. Hoefer (DGH) Foundation and Sentara DGH Comprehensive Breast Center, which provided seed money to support Dr. Tang’s lab in its early days.
Dr. Tang’s research program also has been supported by funding from the Chesapeake Bay Wine Classic Foundation.
Pictured at top: Dr. Amy Tang, seated left, with Dr. Mary Guye; Sentara breast surgeon; Dr. Billur Samli, Sentara breast clinical pathologist; and Patti Bassett, Sentara Pathology laboratory manager. Standing are EVMS MD and PhD students Claire Piatak, Zachary Bouker, Fatima Chaudhry, Jonathan Baker, Nikki Drake and Daniel McWilliams; Darian Hyde, Sentara Pathology technician; and MD student Shoba Abraham. Not present for the photo were Cindy Allen and Dr. Richard Hoefer from Sentara Health Research Center, and Dr. Harry Bear at VCU Massey Cancer Center in Richmond.