Drug sensitivity is affected by alterations of the drug target, such as mutations and/or changes in expression level.104, 108 For instance, 5-FU and pemetrexed treatments inhibit translation of their target mRNA thymidylate synthase (TS),104 thus leading to increased TS expression level and increased 5-FU resistance.104, 105 Moreover, the overexpression and/or oncogenic mutations in many protein tyrosine kinases have been described in human cancers, rendering difficult the anti-protein tyrosine kinase targeting therapies. This evidence concerns the gene TYMS and cancer.