by David Wallace
Researchers have discovered a new therapeutic avenue targeting a protein called RSK1 (ribosomal protein S6 kinase A1), which could revolutionize treatment for blood cancers such as Myeloproliferative Neoplasms (MPN) and secondary Acute Myeloid Leukemia (sAML). This protein plays a crucial role in driving cancer progression and inflammation.
The Drug’s Mechanism
The investigational drug, PMD-026, is a first-in-class oral RSK inhibitor currently in Phase 2 trials for breast cancer. Researchers found that inhibiting RSK1 suppresses inflammation and cancer-promoting signals, effectively reducing disease severity in MPN and sAML models. By blocking the RSK1 pathway, the drug dampens harmful NFκB-mediated inflammation and oncogenic signaling cascades, including PI3K/AKT/mTOR.
This breakthrough highlights the potential of PMD-026 to treat blood cancers by addressing both the cancer cells and their pro-inflammatory environment.
Why This Is Important
Current treatments for MPN and sAML, such as JAK2 inhibitors, primarily manage symptoms but fail to cure the disease or prevent progression to more aggressive forms like sAML. PMD-026 offers a dual benefit:
- Targeting the root drivers of cancer cell growth.
- Reducing inflammation that fuels disease progression.
This innovative approach could transform the standard of care for these challenging blood cancers.
The Research So Far
- Preclinical Studies: Laboratory tests demonstrated that PMD-026 effectively suppresses RSK1 activity, leading to decreased cancer cell survival and inflammation.
- Animal Models: Testing in mouse models of MPN and sAML showed reduced disease burden, including lowered white blood cell counts, suppressed spleen enlargement, and extended survival.
- Clinical Trials: Although initially developed for breast cancer, PMD-026 is being explored for its efficacy in treating myeloid malignancies, with promising early results.
Implications for Patients
For patients with MPN and sAML, PMD-026 could offer:
- Improved survival rates.
- A targeted approach with fewer side effects compared to traditional chemotherapy.
- Hope for those with limited treatment options, especially in advanced stages.
What Comes Next?
Researchers plan to expand clinical trials to confirm the safety and efficacy of PMD-026 in blood cancer patients. Future studies will also explore its potential as a combination therapy with existing treatments, such as JAK inhibitors.
A Glimpse of the Future
This discovery represents a significant step forward in cancer research. By targeting a shared dependency like RSK1, PMD-026 could redefine treatment paradigms for both breast and blood cancers. Ongoing research and clinical trials will determine how this drug can best be integrated into patient care, potentially offering a new lifeline to those battling these diseases.
Reference
Kong, T., Laranjeira, A. B. A., Letson, C. T., et al. (2025). RSK1 is an exploitable dependency in myeloproliferative neoplasms and secondary acute myeloid leukemia. Nature Communications, 16, 492. https://doi.org/10.1038/s41467-024-55643-7
