The predictive biomarkers for antifolate anticancer drugs

我们发现培美曲塞（MTA）和细胞毒性核苷类似物的协同相互作用的机制是多因素的，并且MTA和细胞毒性核苷类似物的组合的化疗活性在改变代谢代谢分子方面是协同的。我们检测了非小细胞肺癌细胞系和用MTA和铂类药物治疗的临床非小细胞肺癌样本中胸苷酸合酶（TS）的拷贝数。在肺癌细胞系和临床NSCLC样本中，TS拷贝数与MTA敏感性之间存在显著相关性。本研究还对ABCC11基因538G>A多态性进行了研究，并建立了表达人ABCC11基因的细胞系，其中一个携带等位基因G，另一个携带等位基因A。此外，我们现在研究ABCC11基因多态性与临床耐药性的MTA之间的关系。

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.