Researchers at VCU Massey Cancer Center have set their sights on a new therapeutic target for an aggressive form of breast cancer with limited treatment options.
Breast cancer is the second most common cancer in U.S. women, and triple-negative breast cancer (TNBC) is a more aggressive and deadly form of disease that accounts for 10-15% of all breast tumors.
TNBC grows and spreads more quickly than other breast tumors and is associated with worse patient outcomes, accounting for nearly one-third of all breast cancer-related deaths.
Additionally, TNBC affects Black women disproportionately: Black women die from TNBC at a significantly higher rate than white women despite being diagnosed at a younger age. Finding an effective therapy that works well in all patients would be an important step in addressing this disparity.
Through a comprehensive and cutting-edge genomic screening method known as CRISPR/CAS9 screening, Massey scientists — led by Anthony Faber, Ph.D., and Jennifer Koblinski, Ph.D. — were able to identify a specific enzyme called UBA1 that revealed itself as an ideal therapeutic target. Using a novel UBA-inhibiting drug called TAK-243, they blocked the cellular function of UBA1 and effectively killed cancer cells in patient-derived breast tumors in mice.
Previous research has shown that UBA1 inhibitors can have a positive impact in hematological cancers such as acute myeloid leukemia (AML) and chronic myelogenous leukemia (CML). This study — recently published in PNAS Nexus — is the first to suggest that UBA1 inhibitors could be effective in TNBC. TAK-243 has been tested recently in early phase trials, paving the way for potential testing in TNBC patients.
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