Current SPORE projects are described below. The grant also funds four Career Enhancement Projects and five Development Research Projects. Five previous CEPs and four previous DRPs have been funded since the SPORE grant was awarded to HCC. Annual requests for proposals are issued for additional CEP & DRPs, usually in the spring.
SPORE
Leukemia
Specialized Programs of Research Excellence
Characterizing Menin Inhibitor Resistance
Specific Aims
- Aim 1: Define the mechanisms of adaptive Menin inhibitor resistance in AML.
- Aim 2: Characterize minimal residual disease (MRD) cells after Menin inhibitor treatment to define mechanisms of therapeutic escape and for comparison to resistant leukemia cells.
- Aim 3: Assess the combination of Menin inhibition with a potent degrader of Ikaros in a clinical trial.
Project Investigators
Targeting PI3 kinase gamma in AML
Specific Aims
- Aim 1: Refine markers for vulnerability and mechanisms of sensitivity to PI3 kinase gamma inhibition in AML.
- Aim 2: Assess PI3 kinase gamma activation and dependency in distinct AML settings and therapy combinations.
- Aim 3: Determine a therapeutic role for PI3 kinase gamma inhibition in AML.
Project Investigators
Targeting the mammalian SWI/SNF (mSWI/SNF) chromatin remodeling complex in AML
Specific Aims
- Aim 1: Define FHD-286-mediated chromatin changes in AML models and primary tumors.
- Aim 2: Determine the impact of SMARACA4/2 inhibition in combination with BCL-2 or FLT3 inhibition in AML models and primary cells.
- Aim 3: Define the clinical impact of FHD-286 in combination with decitabine/venetoclax in treatment-naïve human AML.
