The predictive biomarkers for antifolate anticancer drugs

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We found that the mechanisms of the synergistic interaction of pemetrexed (MTA) and cytotoxic nucleoside analogues are multifactorial, and that the chemotherapeutic activity of the combination of MTA and cytotoxic nucleoside analogues is synergistic with regard to the alteration of metanotbolic molecules.In a search for biomarkers for study of the efficacy of MTA treatment, we examined the thymidylate synthase (TS) copy number in NSCLC cell lines and in clinical NSCLC samples treated with MTA with platinum drugs. Significant correlation was found between the TS copy number and the sensitivity for MTA in both lung cancer cell lines and clinical NSCLC samples. Our results suggest that TS copy number could be a predictive biomarker for MTA.We also focus on ABCC11 polymorphism 538G>A, and established cell liens expressing human ABCC11, one carrying allele G and another carrying allele A. Moreover we now examine the relationship between ABCC11 polymorphism and resistance to MTA clinically.