Dana-Farber Cancer Institute has received USD 2.43 million in first-year funding from the National Cancer Institute (NCI) for a new five-year Specialized Program of Research Excellence (SPORE) focused on translational research in myeloid leukemia.
The multi-project P50 center encompasses three translational research programs, each incorporating planned clinical testing. Principal investigators Andrew A. Lane and Richard M. Stone lead the program, which is anchored within the Dana-Farber/Harvard Cancer Center (DF/HCC) and supported by three shared cores covering biospecimen banking, functional precision medicine, and computational biology.
Each project targets a distinct vulnerability in AML biology. Project 1 investigates resistance mechanisms to menin inhibitors — a class that has drawn substantial industry interest following clinical validation in NPM1-mutant and KMT2A-rearranged AML — and proposes combining them with immunomodulatory imide drugs (IMiDs) in a clinical trial. Project 2 examines PI3 kinase gamma (PI3Kγ) inhibition as a therapeutic strategy, using mechanistic analyses to guide combination regimens and an early-phase trial to assess clinical activity. Project 3 focuses on the mammalian SWI/SNF (mSWI/SNF) chromatin remodeling complex, specifically pharmacologic inhibition of SMARCA4/2 ATPase activity, with a Phase Ib trial planned to evaluate combinations in AML patients.
The mSWI/SNF complex has emerged as a drug target across multiple cancers. Foghorn Therapeutics previously evaluated dual SMARCA4/SMARCA2 ATPase inhibitor FHD-286 in a Phase I study in advanced myeloid malignancies, while its current clinical-stage FHD-909 program selectively targets SMARCA2 in SMARCA4-mutant solid tumors. Menin inhibition is further advanced, with Syndax Pharmaceuticals' revumenib approved in the US for KMT2A-rearranged acute leukemia and NPM1-mutant AML, and Kura Oncology's ziftomenib approved for NPM1-mutant AML.