Research topics - Preclinical evaluation of MAT2A inhibitors for prostate cancer therapy
Castration-resistant prostate cancer (CRPC) is a frequently occurring disease with adverse clinical outcomes and limited therapeutic options. We have recently reported that methionine adenosyl transferase 2a (MAT2A) plays a role in the progression of primary tumors to hormone-refractory prostate cancers. Our data supports that MAT2A is an actionable target in prostate cancer. Genetic and pharmacological inhibition of MAT2A counteract stemness and trans-differentiation in multiple models, reducing tumor sphere formation and organoid growth, restoring androgenic response, and enhancing the response to AR antagonists. Our data indicates a vulnerability of prostate cancer cells to MAT2A inhibition, particularly for tumors with high expression of MAT2A, ERG, and EZH2, like advanced and aggressive ERG-fusion positive CRPC. The overall goal of the proposed experiments is to provide data supporting the feasibility and efficacy of pharmacologic targeting of MAT2A using a MAT2A inhibitor compound in a large set of preclinical models representative of advanced and aggressive prostate cancer. These studies will support the feasibility and specificity of the proposed MAT2A targeted approach.
Sponsored research 2025/2026.
