Groundbreaking research from Washington University School of Medicine in St. Louis is exploring new possibilities for slowing the progression of various blood cancers.
The team’s latest studies center on an existing drug currently evaluated in clinical trials for breast cancer, shedding light on its potential benefits for blood malignancies.
Inhibiting RSK1 for Potential Treatment
The studies, conducted with human patient samples and animal models, propose that inhibiting a protein called RSK1 can reduce inflammation.
This reduction may slow the advancement of myeloproliferative neoplasms (MPNs) and a particularly aggressive form of acute myeloid leukemia (AML).
Since the RSK1 inhibitor is already in clinical testing, researchers are optimistic about its potential to treat blood cancers more effectively.
Publications on this research are forthcoming, with one study slated for release in Nature Communications on January 16, and the other having been published online in Blood Cancer Journal.
Research Findings and Implications
MPNs typically develop slowly and can take years to advance, often requiring continuous monitoring and management of symptoms.
Currently, there are no effective therapies that can halt their progression, making patients vulnerable to developing secondary AML, a more severe type of leukemia with limited treatment options.
Dr. Stephen T. Oh, an associate professor of medicine and co-director of the Division of Hematology at WashU Medicine, leads the research efforts.
He emphasizes the long-term risks faced by patients with chronic MPNs, who may live for decades but are at an increased risk for secondary AML, which usually carries a poor prognosis.
Oh expresses hope that their findings could fill a critical gap in current treatment approaches, targeting not only the prevention of AML but also the ultimate eradication of the disease.
Historically, treatments for MPNs have primarily centered around managing symptoms—like fatigue, night sweats, decreased appetite, weight loss, and splenomegaly—without addressing the core progression of the disease itself or the potential for acute leukemia to develop.
Future Directions and Clinical Trials
The research team believes that RSK1 inhibitors could empower patients with chronic MPNs to improve their health enough to be considered for stem cell transplants.
Such transplants can offer long-lasting remission for various blood cancers. Dr. Oh, who treats patients with these conditions at the Siteman Cancer Center, linked to Barnes-Jewish Hospital and WashU Medicine, sees a real opportunity for progress.
In the study featured in Nature Communications, the team found that blocking RSK1 significantly reversed MPN symptoms in murine models, leading to substantial reductions in fibrotic changes in the bone marrow and cancerous cell populations—by as much as 96%—over a four-week treatment period.
These findings also indicated a promising capacity to prevent the chronic condition from advancing to secondary AML.
Meanwhile, the research published in Blood Cancer Journal showcased the effectiveness of RSK1 inhibition against FLT3-ITD AML, which can occur independently of MPNs.
While there are existing FLT3 inhibitors, resistance is a common challenge.
Researchers suspect that the RSK1 inhibitor may circumvent this issue by impacting alternate pathways.
The RSK1 inhibitor utilized in these investigations, known as PMD-026, is administered orally and is currently being tested for breast cancer.
Early results show that participants with metastatic breast cancer have tolerated the drug well, experiencing only mild side effects.
Dr. Oh’s previous research identified DUSP6 as a critical signaling molecule linked to MPN progression.
This led to discoveries about downstream signals initiated by DUSP6, with RSK1 emerging as a key intervention target through the RSK1 inhibitor being tested.
PMD-026 acts as a pan-RSK inhibitor, targeting all four members of the RSK protein family: RSK1, RSK2, RSK3, and RSK4.
Initial data suggest it primarily inhibits RSK2 in the context of breast cancer.
If PMD-026 gains FDA approval for breast cancer treatment, it could become the first drug specifically targeting the RSK protein family available on the market.
This could pave the way for more targeted therapies that disrupt RSK-driven cancer progression.
Additionally, research on PMD-026 may provide new insights into targeting cancer by highlighting the role of RSK inhibition in tumor growth and resistance mechanisms.
As further clinical studies validate its efficacy, PMD-026 has the potential to set a precedent for developing next-generation RSK-specific inhibitors in oncology.
Dr. Oh and his collaborators, including Tim Kong, a leading author of both studies and an MD-PhD student in his lab, are excited about their partnership with Phoenix Molecular Designs, the biotechnology firm behind the drug.
Collaboratively, they identified RSK1’s essential role across multiple blood cancers and hypothesized that PMD-026 could effectively hinder its activity.
The researchers are enthusiastic about the implications of their findings for future clinical trials, seeing RSK1 as a novel therapeutic target for MPNs and AML.
They are designing a clinical trial framework aimed at patients who have already exhausted standard therapies for chronic MPN and may not be eligible for stem cell transplants due to age or overall health conditions.
Source: ScienceDaily