A researcher at the University of Houston College of Pharmacy Drug Discovery Institute is working to revolutionize treatment regimens for triple-negative breast cancer (TNBC) by proving that nebivolol, an FDA-approved drug for high blood pressure, is effective in treating it. Meghana Trivedi, professor of Pharmacy and Pharmacology, has been awarded $1.1 million by the U.S. Army Medical Research Acquisition Activity to support her work.
In the world of breast cancer, the kind termed 'triple-negative' dangerously lives up to its name – it grows aggressively, is more likely to have spread by the time it's discovered and will commonly return after treatment. Still, the name triple-negative means something else, referring to tumors that test negative for estrogen receptors (ER), progesterone receptors (PR) and excess HER2 protein.
Worse still, effective treatments for most breast cancers block the growth-stimulating effects of ER PR and/or HER2, leaving the deadly TNBC with few choices for treatment. Because TNBC lacks specific targets, it is mostly managed by general chemotherapy.
"We believe that our studies will demonstrate that nebivolol can be used as an easily available and economically viable treatment in TNBC patients," said Trivedi. "Our research will investigate preclinical efficacy as well as pharmacokinetics of nebivolol and mechanism of action by which it exerts its anti-cancer activity in TNBC."
In preliminary studies, Trivedi identified a few potential drugs that target G protein-coupled receptors (GPCRs) for treating TNBC. GPCRs are excellent targets because the drugs targeting them generally have good safety profiles and are used for many chronic diseases including high blood pressure, heart failure, kidney diseases, allergies, heartburn, Alzheimer's disease and depression among others. In fact, 30-50% of all FDA-approved drugs target GPCRs. A major focus in Trivedi's laboratory research is to identify GPCR targets and drugs in treatment of breast cancer and other types of cancer.
"If we can repurpose these drugs that have already proven to be safe for human use, we can make them available to TNBC patients faster," 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 patients with early-stage TNBC progress to metastatic recurrence in other organs within the first five years of treatment. Patients with metastatic TNBC die prematurely, with median survival of only 12 months," she said.
Trivedi's team includes Chad Creighton and Benny Kaipparettu from Baylor College of Medicine, and from the University of Houston, Diana S-L Chow and Michael Johnson.
