Pulmonary hypertension (PH) raises pressure levels in the vessels that carry blood from the heart to the lungs. That forces the heart to work in overdrive, which can lead to heart failure, multi-organ dysfunction and sometimes death. Existing methods of treating PH are sometimes ineffective and hard for patients to tolerate.
Knowing there are some similarities in gene-expression patterns between PH and cancer, researchers at the University of Pittsburgh School of Medicine (UPMC) and Prairie View A&M University set out to find cancer drugs that might also address the lung disorder. Using a computational platform they developed, they uncovered two promising compounds, one of which reversed symptoms of PH in rodent models, the researchers reported in Science Advances.
UPMC’s Stephen Chan, M.D., Ph.D., director of Pitt’s Vascular Medicine Institute, partnered with Seungchan Kim, Ph.D., a chief scientist and electrical and computer engineering professor at Prairie View, to build a computational platform analyzing gene expression data from 800 cancer cell lines. They exposed those cells to various oncology treatments.
The goal was to figure out which ones correlated with PH-specific gene networks, the team explained. They ranked each drug on its ability to rewire PH-specific gene networks, and two compounds shot to the top of the charts: I-BET762 and BRD2889. I-BET762 is a member of the bromodomain and extra-terminal (BET) inhibitor class, while BRD2889 is a plant-derived compound with known anti-cancer properties.
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GlaxoSmithKline studied I-BET762 in multiple early-stage cancer trials, some of which were withdrawn, according to ClinicalTrials.gov. The compound no longer shows up on GSK’s pipeline, and other companies have abandoned their experimental BET inhibitors, including Roche.
BET is still a target of interest in cancer and other diseases, including lung disease. Reservlogix is evaluating BET inhibitor apabetalone as a potential treatment, on top of standard of care, for pulmonary arterial hypertension in a phase 2 study.
As for the other compound that turned up in the new study, BRD2889, it's an analog of a compound taken from long pepper plants. It has not yet been studied in patients with PH, the UPMC and Prairie View researchers said.
In mice and rat models of PH, BRD2889 reversed symptoms, the researchers reported in the study. That gave them hope for its potential use as a new treatment for PH, and they filed for a patent with the goal of moving the compound into human trials.
The researchers will look at other compounds with potential promise in PH, because repurposing drugs can help tamp down the cost and time it takes to create new treatments, they said. “With this algorithm in hand, we may be able to repurpose existing cancer drugs for the treatment of other rare and emerging diseases,” Chan said in a statement.