| abstract |
The present invention is directed to combination therapies fro treating cell proliferative disorders associated with methylthioadenosine phosphorylase (MTAP) deficient cells in a mammal. The combination therapies selectively kill MTAP-deficient cells by administering an ihibitor of de novo inosinate synthesis and administering an anti-toxicity agent, wherein the inhibitors of de novo inosinate synthesis are inhibitors of glycinamide ribonucleotide formyltransferase ('GARFT') and/or aminoinidazolecarboximide ribonucleotide formyltransferase ('AICARFT'), and the anti-toxicity agent is an MTAP substrate (e.g. methylthioadenosine or 'MTA'), a precursor of MTA, an analog of an MTA precursor or a prodrug of an MTAP substrate. |