Recent research from Washington University School of Medicine (WashU Medicine) suggests a potential breakthrough in the treatment of myeloproliferative neoplasms (MPNs) and acute myeloid leukaemia (AML). Researchers discovered that PMD-026, a medication now in clinical trials for breast cancer, could also be useful in treating these blood malignancies. This study examines the findings and discusses their implications for future therapies. 

MPNs are slow-growing blood malignancies that can last for years but frequently progress to secondary AML, a very aggressive and treatment-resistant leukaemia. Patients with chronic MPNs have few treatment choices, which mostly focus on symptom control rather than disease progression. As Stephen Oh, MD, PhD, points out, "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." The scarcity of successful treatments highlights the importance of identifying new therapeutic procedures.

The two studies, which were published in Nature Communications and Blood Cancer Journal, show that blocking the RSK1 protein can help treat MPNs and AML. The study found that inhibiting RSK1 decreases inflammation and stops disease development. 

In the Nature Communications study, researchers evaluated the RSK1 inhibitor on MPN-infected mouse models. The findings were promising, indicating that "inhibiting RSK1 eliminated up to 96% of cancer in mice after four weeks." Furthermore, the medication reduced fibrosis in the bone marrow, a significant indicator of disease development. 

The Blood Cancer Journal study expanded on these findings to include the FLT3-ITD AML subtype. Usually, FLT3 inhibitors treat this type of leukaemia; however, resistance to these medications develops over time. Their idea was that "because the RSK1 inhibitor blocks a different pathway," it could be used as an alternative for AML cases that don't respond to other treatments. 

A new drug called PMD-026 is being tested. It is a pan-RSK inhibitor, which means it works on all four types of the RSK protein. In breast cancer studies, it has demonstrated tolerance with "low-grade side effects." PMD-026's potential to inhibit RSK1 activity in MPNs and AML gives it a strong candidate for repurposing. 

One of the primary advantages of this medicine is its ability to prepare MPN patients for stem cell transplantation. Oh explains, "Theoretically, treating people with chronic MPNs with RSK1 inhibitors could make their health better enough that they could be eligible for a stem cell transplant. This is the best treatment for many blood cancers because it can lead to long-term remission." 

However, issues remain. While the medicine has performed well in breast cancer trials, its long-term efficacy and safety in blood cancer patients require further investigation. Furthermore, identifying the ideal patient population for clinical trials is critical. Oh remarked, "We are contemplating a few situations for designing a future clinical trial. It will most likely be for individuals who have progressed beyond the usual medications used for the chronic phase of this disease but are not eligible for stem cell transplantation due to age or general health." 

The discovery of RSK1 as a target for blood cancer treatment marks a significant milestone in oncology. By repurposing PMD-026, researchers are paving the way for new clinical applications. Collaborations between WashU Medicine and Phoenix Molecular Designs demonstrate the research's translational potential. 

This study not only offers hope to MPN and AML patients; it also emphasises the need for targeted medicines in oncology. Future clinical trials will evaluate whether PMD-026 can become an approved medication, thereby closing a critical gap in blood cancer care. According to Oh: "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."