Pemetrexed is an anticancer drug primarily used for the treatment of pleural mesothelioma and non-small cell lung cancer. It is a multi-targeted antifolate compound i.e. it inhibits many of the key enzymes (thymidylate synthase (TS) and dihydrofolate reductase (DHFR), glycinamide ribonucleotide formyl transferase (GARFT) and aminoimidazole carboxamide formyl transferase) involved in folic acid metabolism.
TS activity increase significantly in rapidly proliferating cells, so these can be the potential targets for cancer treatment. You can work on different ways of reducing its activity or determining its increased activity for more options of treatment and diagnosis respectively.
You can also work on the relation of TS with epidermal growth factor receptor (EGFR) for enhanced treatment of cancer, which are involved in many cellular functions and are overly expressed in solid tumors.
Researchers have found that pemetrexed treated patients respond differently to the drug such as patients with “MTHFR C677T had longer survival compared with patients with other genotypes”. They are of the opinion that more research is needed in Asian patients in relation to folate metabolism and the efficacy of antifolate compounds. Moreover, “further validation and investigation of the efficacy of pemetrexed according to the classification of TS genotypes are needed.”
More “prospective studies will be needed to find a genetic marker that can be used in clinical practice to individualized drug therapy in NSCLC patients,” Researchers concluded.
Jung M, Lee CH, Park HS, Lee JH, Kang YA, Kim SK, Chang J, Kim DJ, Rha SY, Kim JH, & Cho BC (2013). Pharmacogenomic assessment of outcomes of pemetrexed-treated patients with adenocarcinoma of the lung. Yonsei medical journal, 54 (4), 854-64 PMID: 23709418