Therefore, we hypothesize that MTAP loss produces a synthetic lethal vulnerability to de novo adenine synthesis inhibition thus rendering MTAP-deficient (MTAPdef) tumor cells susceptible to antifolate agents (Fig. 1a) including pemetrexed, which is a potent antifolate agent that suppresses de novo purine synthesis (as well as thymidine synthesis) by inhibiting three of the key enzymes involved in folate metabolism, namely dihydrofolate reductase, thymidylate synthase, and glycinamide ribonucleotide formyl transferase28. The gene discussed is MTAP; the disease is neoplasm.