Computer Program Finds New Applications for Old Medications

Non-steroidal anti-inflammatory drugs (NSAIDs) are neither new nor novel, but that doesn’t mean science has already found every way that they can benefit patients. A computer program developed at Case Western Reserve University, called DrugPredict, that can look for new uses for old drugs.

The program’s creators recently teamed up with oncological researchers to apply laboratory scrutiny to DrugPredict’s predictive prowess. In a newly-published study, they demonstrate how the program may have correctly determined the usefulness of NSAIDs in the fight against epithelial ovarian cancer.

The platform works by searching through thousands of FDA-approved drugs, looking at their chemical compounds, phenotypes, and genetic factors to pair them with diseases where they may be applicable. Because drug discovery is typically a long and expensive process, tools like DrugPredict could be useful in leveraging medicines that have already been found safe.

"For any given disease, DrugPredict simultaneously performs both a target-based, and phenotypic screening of over half a million chemicals, all in just a few minutes,” Rong Xu, PhD, said. Xu, one of the program’s co-developers, is an associate professor of biomedical informatics in the department of population and quantitative health sciences at Case Western Reserve University School of Medicine.

For this study, the program crunched out a list of nearly 7,000 chemicals that showed promise for treating epithelial ovarian cancer. Over 1,000 FDA-approved drugs appeared on the list. Other than 15 existing cancer treatments that appeared at the top, NSAIDs consistently outranked every other class of FDA-approved drugs that DrugPredict recommended.

Laboratory testing showed that one NSAID, indomethacin, may be particularly effective. Their work found that the drug “inhibits cell proliferation, cell survival and induces robust cell death in cisplatin-resistant cells and [tumor-initiating cells].” Cisplatin is a commonly-used chemotherapy drug, and the researchers suggest their lab results showed that indomethacin may be an effective adjuvant to the therapy.

By combining DrugPredict with laboratory expertise, “We were able to uncover a potentially novel drug approach to treat ovarian cancer,” Analisa DiFeo, PhD, of the Case Comprehensive Cancer Center at Case Western Reserve University School of Medicine said. "Our results provide a rationale to test NSAIDs like Indomethacin as a novel drug in ovarian cancer clinical trials."

According to the statement, DiFeo will do just that: she is currently planning a phase 1 clinical trial to test indomethacin’s ability to target ovarian cancer stem cells in patient tumors.

The study, “Using a novel computational drug-repositioning approach (DrugPredict) to rapidly identify potent drug candidates for cancer treatment,” was published recently in Nature Oncogene.