pemetrexed + sirolimus

Pemetrexed + sirolimus is an investigational combination therapy evaluated primarily for the treatment of advanced non-squamous non-small cell lung cancer (NSCLC), particularly in patients with recurrent or metastatic disease. Pemetrexed is a multitargeted antifolate chemotherapeutic agent that inhibits enzymes involved in purine and pyrimidine synthesis, including thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT). Sirolimus is an oral inhibitor of the mammalian target of rapamycin (mTOR) pathway, which regulates cell growth and proliferation. Preclinical studies demonstrated synergistic anti-tumor effects when these agents are combined, likely due to mTOR inhibition enhancing chemotherapy response by downregulating resistance mechanisms such as TS expression. Clinical trials have shown that this combination can be active in heavily pretreated NSCLC patients, with manageable toxicity at defined maximum tolerated doses[1][3][6][8].

Other names

pemetrexed and sirolimusP + S