Grant Awarded to Study Some of the Most Fatal Forms of Cancers

Cancer researchers Jenny C. Chang, MD, and Jing Yang, PhD, received a combined total of $500,000 from the Cancer Prevention and Research Institute of Texas (CPRIT) to study difficult-to-treat cancers that are often fatal.

Chang received a $250,000 grant to study the links between nitric oxide synthase (NOS) and obesity in triple-negative breast cancer (TNBC).

“Successful completion of their proposed work will provide an improved understanding of the role of the NOS inhibitors in TNBC and may define prognostic markers in obese TNBC patients at a higher risk of mortality,” the researchers said in a press release.

TNBC considerably has the worst outcomes out of any subtype of breast cancer. Chang noted it can be more resistant to chemotherapy and patients have an increased risk of relapse and death. Obese patients are even more likely to suffer from worse outcomes with TNBC.

Previous research found that obesity can reprogram the tumor microenvironment. The reprogramming of this environment can result in greater NO levels, which Chang said are associated with chronic inflammation. Tumor neutrophil infiltration is also associated with chronic inflammation, which may cause increased metastasis of TNBC, possibly leading to worse outcomes among patients with obesity.

Chang and team suggest that inhibiting NOS can enhance the efficacy of current TNBC standard of care. Knowledge of NOS inhibitors in TNBC might also, “enhance the appropriate selection of TNBC patients who would benefit from chemotherapy and/or immune checkpoint therapy,” the authors wrote in the press release.

Yang received $250,000 to study multiple myeloma and find more effective treatments and improve survival. More specifically, Yang and team will look at daratumumab (DARA), an FDA-approved monoclonal antibody treatment.

“The knowledge gained from their study should uncover innovative insight into how multiple myeloma cells escape from DARA treatment,” the researchers said in the release.

Multiple myeloma is one of the most common forms of blood cancer. Yang said that DARA, while proven effective as a combination treatment, is not always successful for high-risk patients with multiple myeloma. Yang and team found that patients express the NHE6 protein at elevated rates, and it could make them less responsive to DARA.

Yang and team will study DARA resistance that occurs from high levels of NHE6 expression to improve DARA efficacy. They predict that “targeting NHE6 and developing an inhibitor to do so could significantly improve DARA-based multiple myeloma therapy outcomes,” the researchers said.

Chang is the director of Houston Methodist Dr. Mary and Ron Neal Cancer Center and Emily Hermann Chair in Cancer. Yang is an associate professor of oncology at the Houston Methodist Research Institute and member of the Houston Methodist Neal Cancer Center.

Reference

Houston Methodist. Taking aim at triple-negative breast cancer and multiple myeloma to improve prognoses. EurekAlert! September 27, 2022. Accessed on September 27, 2022. https://www.eurekalert.org/news-releases/966030