Indeed, in advanced or metastatic NSCLC, a phase I/II study of pemetrexed (an inhibitor of thymidylate synthase dihydrofolate reductase and glycinamide ribonucleotide formyltransferase) with or without the combination of ABT-751 treatment was not able to improve the progression-free survival. This evidence concerns the gene DHFR and non-small cell lung carcinoma.