This $467,492 federal Project Grant award from the National Cancer Institute (CFDA 93.395 - Cancer Treatment Research) supports research at Mayo Clinic to advance the treatment of therapy-related myeloid neoplasms (TMNs), including myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), that can develop in ovarian cancer patients treated with PARP inhibitors.
The research aims to: 1) further define the mechanisms by which replication checkpoint modulators induce apoptosis in TP53-mutant AML, 2) evaluate the antineoplastic effects of replication checkpoint modulators, alone and in combination with other agents, on PARP inhibitor-emergent TMN samples from ovarian cancer patients, and 3) assess the efficacy of replication checkpoint modulators in patient-derived xenograft models of PARP inhibitor-emergent AML. This research is intended to provide insights to support a future early-phase clinical trial of replication checkpoint modulator-based therapy for ovarian cancer patients with PARP inhibitor-associated TMNs, which represent a significant unmet medical need.