FDA Investigates Repurposing a Diabetes Drug to Overcome Chemoresistance in NSCLC

By: Celeste L. Dixon
Posted: Friday, August 2, 2024

Evidence that epalrestat, an extant drug used abroad to treat diabetic neuropathy, may overcome drug resistance in non–small cell lung cancer (NSCLC) has been published in Clinical Cancer Research and is part of the reason the drug is being considered by the U.S. Food and Drug Administration (FDA) for approval in this setting. Jussuf T. Kaifi, MD, PhD, of the University of Missouri, Columbia, and colleagues found that chemoresistant NSCLC tumor tissues demonstrated overexpression of the enzyme aldo-keto reductase 1B10 (AKR1B10); epalrestat is an oral AKR1B10 inhibitor.

For their research, the team used patient-derived tumor organoids and matched tumor tissues from 10 patients with nonmetastatic stage I to IIIA NSCLC who, prior to surgical resection, were treatment-naive. The tumors of five patients were found to be resistant to standard-of-care platinum-based doublet chemotherapy, with tumor organoids and matched tissues demonstrating AKR1B10 overexpression. All patients were prospectively enrolled and observed for at least 2.5 years.

“The in vivo efficacy of epalrestat to overcome drug resistance corresponded to intratumoral epalrestat levels,” explained the investigators, adding that the agent is suitable for the clinical trials the FDA is now undertaking because of its favorable toxicity, pharmacologic profile, and bioavailability. Also, epalrestat penetrates the brain, which is among “the most common and devastating metastatic sites of NSCLC,” they declared.

With FDA approval, epalrestat could be fast-tracked for use in treating lung cancer, Dr. Kaifi said in an institutional press release. “In general, developing new drugs for cancer treatment is an extremely lengthy, expensive, and inefficient process,” he explained. “In contrast, ‘repurposing’ [drugs already approved for] other diseases is much faster and cheaper. In view of overcoming drug resistance, [hopefully] epalrestat can rapidly be advanced to the clinic to improve cure rates in lung cancer patients.”

Disclosure: For full disclosures of the study authors, visit aacrjournals.org.

Clinical Cancer Research

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