Investigational Breast Cancer Drug Demonstrates Potential Benefit in Treating AML and Other Blood Cancers

Researchers at Washington University School of Medicine in St. Louis, MO, have discovered a way to repurpose a breast cancer study drug to potentially treat two types of blood cancer. Drug repurposing offers an attractive path in research, as it may shorten the roadway to approval by regulatory agencies.

The investigational drug, called PMD-026, is currently in phase 2 clinical trials for the treatment of breast cancer. PMD-026 is a potential first-in-class oral pan-RSK inhibitor targeting the proteins RSK1, RSK2, RSK3, and RSK4. Studies suggest that blocking RSK2 may be beneficial in treating breast cancer. For blood cancers, RSK1 is the target of interest.

Two studies led by Tim Kong, MD-PhD student at Washington University School of Medicine, found that blocking RSK1 reduces inflammation and may inhibit the progression of myeloproliferative neoplasms (MPNs) and acute myeloid leukemia (AML).

MPNs are a group of slow-growing blood cancers that cause the bone marrow to produce too many red blood cells, white blood cells, or platelets. There is no treatment to slow the disease progression, and people with MPNs have a high risk of developing AML.

Currently approved treatments for AML include FLT3 inhibitors Rydapt (midostaurin), Vanflyta (quizartinib), and Xospata (gilteritinib). However, resistance to the drugs’ mechanism frequently develops.

One of the studies published today in Nature Communications found that inhibiting RSK1 reversed MPN progression and removed 96% of cancer in mice. Kong and others in his research group hope that blocking RSK1 with PMD-026 could prevent people with MPNs from developing AML. Ideally, this treatment would ameliorate patients’ health status enough to enable them to be eligible for stem cell transplant.

“Patients with chronic MPNs can live with the disease sometimes for decades, but they’re at increased risk of developing secondary AML, which has a poor prognosis,” senior author Stephen T. Oh, M.D., Ph.D., associate professor of medicine and co-director of the division of hematology at Washington University School of Medicine, said in a press release.

“These patients have no effective medical therapies, so we hope this new drug will help fill that gap in clinical care. At minimum, we’re hopeful this drug can stop the chronic disease from progressing to AML. But the goal is to eliminate the disease and get patients into remission,” he added.

The second study, published in the November 2024 issue of the Blood Cancer Journal, found that inhibiting RSK1 could be therapeutic in treating AML with FLT3 internal tandem duplication (FLT3-ITD) mutation. FLT3-ITD AML is an aggressive blood cancer with an overall poor prognosis. According to the researchers, by blocking RSK1 instead of FLT3, PMD-026 could potentially address the drug resistance associated with currently available AML treatments.

Kong and his team are eager to proceed with clinical trials for PMD-026 in the blood cancer space. “We are excited about these studies because they highlight RSK1 as a novel therapeutic target for MPNs and AML with a viable strategy for moving an investigational drug into clinical trials in the near future,” commented Oh.

Phoenix Molecular Designs, a biotechnology company headquartered in Vancouver, BC, Canada, is developing PMD-026.