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MPN Workshop of the Carolinas 2025 | RSK1 as an exploitable dependency in MPNs and secondary AML
Stephen Oh, MD, PhD, Washington University School of Medicine, St. Louis, MO, discusses RSK1 as an exploitable dependency in myeloproliferative neoplasms (MPNs) and secondary acute myeloid leukemia (AML), particularly in the setting of disease progression. Prof. Oh highlights the effectiveness of genetic and pharmacological targeting of RSK1 in preclinical models and mentions the oral kinase inhibitor PMD-026, which is currently being investigated in a Phase II study for breast cancer and is expected to be tested in an investigator-initiated study for myelofibrosis and other advanced myeloid malignancies. This interview took place at the 2nd Annual MPN Workshop of the Carolinas, held in Charlotte, NC.
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Transcript
So we’ve been investigating the role of RSK1 in myeloproliferative diseases and secondary AML, and we’ve found that this seems to be an exploitable dependency across myeloid neoplasms, so including MPNs as well as other myeloid malignancies, and particularly in the setting of disease progression. Yeah, so we found that both genetic and pharmacologic targeting of RSK1 has been effective in our preclinical models...
So we’ve been investigating the role of RSK1 in myeloproliferative diseases and secondary AML, and we’ve found that this seems to be an exploitable dependency across myeloid neoplasms, so including MPNs as well as other myeloid malignancies, and particularly in the setting of disease progression. Yeah, so we found that both genetic and pharmacologic targeting of RSK1 has been effective in our preclinical models. We utilize animal models such as the MPL retroviral transplant system, as well as patient-derived xenograft models, and consistently targeting RSK1, for instance, with PMD-026, which is an oral kinase inhibitor, has been able to ameliorate disease phenotypes in these settings.
Yeah, so the compound PMD-026, which is being developed by a company called Phoenix Molecular Designs, has been in development for breast cancer and is currently in a Phase II study for breast cancer. We’ve been working closely with Phoenix Molecular Designs and we’re actually on the cusp of initiating an investigator-initiated study in myelofibrosis and other advanced myeloid malignancies with this compound, PMD-026. So I think it’s important to note that, again, this drug is in development for breast cancer. This will be, our study will be the first study to investigate this compound in hematologic malignancies, and so we have some experience to draw on from the breast cancer study, but we’ll see how this pans out in this setting.
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