Inhibition of BBOX1 Enzyme Might Be Effective Therapeutic Approach in Triple-Negative Breast Cancer

One member of a larger family of oxygen-sensing enzymes could offer a viable target for triple-negative breast cancer (TNBC) therapy, researchers from the University of Texas Southwestern (UTSW) report in a new study. The findings, published online on July 20, 2020 in Cancer Discovery, might offer hope to this subset of patients who have few effective treatment options and often face a poor prognosis. The article is titled “Identification of BBOX1 as a Therapeutic Target in Triple-Negative Breast Cancer.” TNBC – so called because it lacks estrogen receptors, progesterone receptors, and overexpression of the growth-promoting protein HER2 – makes up only 15 to 20 percent of all breast cancers. However, explains Qing Zhang, PhD, Associate Professor in the Department of Pathology at UTSW and a Cancer Prevention and Research Institute of Texas (CPRIT) Scholar in Cancer Research, it’s the deadliest of all breast cancers, with a five-year survival rate of 77 percent compared with 93 percent for other types. Unlike other cancers which are hormone receptor or HER2 positive, TNBC has no targeted treatments, so patients must rely only on surgery, chemotherapy, and radiation, which are less effective than targeted treatments and can harm healthy tissue. Dr. Zhang’s lab studies how cancers can thrive in low-oxygen environments. Looking for viable drug targets for TNBC, Dr. Zhang and his colleagues zeroed in on 2-oxoglutarate (2OG)-dependent enzymes, a family of 70 enzymes including some that function as oxygen sensors in cells. To determine their role in TNBC, the researchers used a library of short interfering RNAs (siRNAs)--snippets of genetic material that can shut off the expression of specific genes--to individually turn off each member of the 2-OG-dependent family in different TNBC and healthy breast cell lines.
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