Two groundbreaking studies conducted by researchers at Washington University School of Medicine in St. Louis have identified a promising approach to halting the progression of several forms of blood cancer using a drug currently in clinical trials for breast cancer. The studies, conducted using patient samples and animal models, demonstrate that inhibiting a protein called RSK1 significantly reduces inflammation and prevents the progression of myeloproliferative neoplasms (MPNs) and an aggressive type of acute myeloid leukemia (AML). The RSK1 inhibitor, already in clinical testing, could expedite the pathway to treating these blood cancers.
The first study was published on January 16 in Nature Communications, while the second study appeared in the Blood Cancer Journal.
Blood Cancer Challenges and the Need for Novel Therapies
MPNs are chronic blood cancers that can persist for years, allowing patients to manage symptoms but with limited options to slow disease progression. These conditions place patients at a heightened risk of developing secondary AML, a highly aggressive form of leukemia with no effective treatments.
“Patients with chronic MPNs can sometimes live with the disease for decades, but the risk of secondary AML—which carries a poor prognosis—is a constant concern,” explained Dr. Stephen T. Oh, MD, PhD, senior author of the studies and co-director of the Division of Hematology at Washington University School of Medicine. “There are currently no effective therapies to stop MPN progression or reduce the risk of transformation into AML. This new drug offers hope for filling that gap in clinical care.”
Current treatments for MPNs focus on managing symptoms such as severe fatigue, night sweats, weight loss, poor appetite, and an enlarged spleen. However, these therapies do not address the underlying disease mechanisms or prevent progression. By targeting RSK1, researchers believe they have identified a novel therapeutic avenue that could halt or even reverse disease progression, potentially allowing patients to qualify for stem cell transplantation, the only curative option for many blood cancers.
Study Findings and Implications
In the Nature Communications study, researchers demonstrated that inhibiting RSK1 reversed MPN progression in mouse models. The treatment reduced bone marrow fibrosis (scarring) and eliminated up to 96% of cancer cells in just four weeks. Moreover, the drug showed potential in preventing chronic MPNs from progressing to secondary AML.
The second study, published in the Blood Cancer Journal, focused on a specific form of AML known as FLT3-ITD AML, which arises independently of MPNs. While FLT3 inhibitors are commonly used to treat this aggressive leukemia, the cancer often develops resistance over time. By targeting RSK1, which operates through a different pathway, the investigational drug could overcome this resistance and provide a new therapeutic option for patients.
The drug used in these studies, PMD-026, is a pan-RSK inhibitor that blocks all four versions of the RSK protein family (RSK1, RSK2, RSK3, and RSK4). Early trials for metastatic breast cancer have shown that PMD-026 is well-tolerated, with manageable side effects. If approved by the FDA, it would be the first drug targeting the RSK family of proteins.
A Collaborative Path to Clinical Trials
Dr. Oh’s team became interested in PMD-026 after identifying RSK1 as a key driver of MPNs and certain forms of AML. In collaboration with Phoenix Molecular Designs, the biotech company that developed the drug, the researchers tested PMD-026 in preclinical models to evaluate its potential efficacy in blood cancers.
“These studies highlight RSK1 as a novel therapeutic target for MPNs and AML,” said Oh. “The availability of an investigational drug already in clinical trials accelerates our ability to design studies for blood cancer patients. We’re exploring trial designs for patients who have exhausted standard therapies but are not eligible for stem cell transplantation due to age or health issues.”
Broader Implications for Blood Cancer Treatment
A key finding from the studies is the role of RSK1 in driving inflammation and disease progression in blood cancers. An earlier study by Oh’s group identified a signaling molecule called DUSP6 as a critical driver of MPNs. Further research revealed that RSK1 acts downstream of DUSP6, making it an ideal target for intervention. By blocking RSK1, PMD-026 interrupts the disease pathway, offering a dual benefit of reducing inflammation and halting cancer progression.
The investigational drug’s ability to improve patient health to the point where they can undergo stem cell transplantation is particularly promising. Transplants offer the potential for long-term remission but are often inaccessible to patients with advanced disease or poor health. By stabilizing or reversing disease progression, RSK1 inhibitors could make this life-saving procedure a viable option for more patients.
Designing Future Clinical Trials
Oh and his team are now focused on translating these preclinical findings into clinical trials. Potential trial participants would include patients with advanced MPNs who have not responded to standard therapies but are not eligible for transplantation. Additionally, trials may target AML patients who have developed resistance to existing treatments.
We’re optimistic about the potential of PMD-026 to change the treatment landscape for these blood cancers,” said Oh. “Our goal is not only to stop disease progression but to achieve remission and improve quality of life for patients.
Read more: Experimental Breast Cancer Drug Shows Potential to Treat Certain Blood Cancers
