A University of Houston College of Pharmacy Drug Discovery Institute researcher is working to revolutionize the treatment of triple-negative breast cancer (TNBC) by demonstrating that nebivolol, an FDA-approved drug for high blood pressure, is effective in treating it. Meghna Trivedi, professor of pharmacy and pharmacology, has been awarded $1.1 million by the US Army Medical Research Acquisition Activity to support her work.
In the world of breast cancer, the ‘triple-negative’ type dangerously lives up to its name – it grows aggressively, is more likely to spread by the time it’s discovered, and will usually return after treatment. However, the name triple-negative means something else, that tumors test negative for estrogen receptor (ER), progesterone receptor (PR) and additional HER2 protein.
Worse, effective treatments for most breast cancers inhibit the growth-promoting effects of ER PR and/or HER2, leaving malignant TNBC with few options for treatment. Because TNBC lacks specific targets, it is mostly managed with simple chemotherapy.
We believe that our studies will show that nebivolol can be used as a readily available and cost-effective treatment in TNBC patients. Our research will investigate the preclinical efficacy as well as the pharmacokinetics of nebivolol and the mechanism of action by which it exerts anti-cancer activity in TNBC.”
Meghna Trivedi, Professor of Pharmacy and Pharmacology, University of Houston
In preliminary studies, Trivedi has identified several potential drugs targeting G protein-coupled receptors (GPCRs) to treat TNBC. GPCRs are excellent targets because drugs targeting them generally have good safety profiles and are used for many chronic diseases, including high blood pressure, heart failure, kidney disease, allergies, heartburn, Alzheimer’s disease, and depression, among others. In fact, 30-50% of all FDA-approved drugs target GPCRs. A major focus of research in Trivedi’s laboratory is identifying GPCR targets and drugs to treat breast cancer and other types of cancer.
“If we can repurpose these drugs that have already been proven safe for human use, we can quickly make them available to TNBC patients,” said Trivedi. “Surprisingly, GPCRs are virtually unexplored as drug targets in breast cancer, and there is an urgent clinical need to identify novel treatments for TNBC that are both safe and effective.”
“At least one-third of early-stage TNBC patients progress to metastatic recurrence in other organs within the first five years of treatment. Metastatic TNBC patients die prematurely, with survival of only 12 months,” he said.
Trivedi’s team includes Chad Creighton and Benny Kaiparettu of Baylor College of Medicine, and Diana SL Chow and Michael Johnson of the University of Houston.