A novel therapeutic drug for selective treatment of castration-resistant prostate cancer with MTAP deficiency
Chemotherapy is currently the most effective approach for treatment of advanced cancer. However, chemotherapeutics do not differentiate between malignant and normal cells, and lead to serious side effects. Recent findings indicate that a substantial proportion of cancers, as distinct from normal tissue, are deficient in an enzyme called methylthioadenosine phosphorylase (MTAP). This provides a unique opportunity for developing chemotherapeutics to treat MTAP-deficient malignancies and simultaneously protect normal tissue by co-administration of 5'-deoxy-5'-methylthioadenosine (MTA), an MTAP substrate present in normal tissues. In preliminary studies we have shown that this is feasible. Here we propose to evaluate this strategy using clinically relevant, patient-derived cancer xenograft models. This approach will benefit patients with MTAP-deficient malignancies. The project will serve as a bridge between academia and the pharmaceutical industry and be beneficial for the career development of the interns in charge and may lead to new, effective cancer treatments/patents also benefiting the partner organization.