On the other hand, we showed effective target engagement in the mesothelioma cell lines, in that pem treatment increased the amount of unused purine and pyrimidine, consequent to the impaired DNA and RNA synthesis (subsequent to the inhibition of thymidylate synthase, dihydrofolate reductase and glycinamide ribonucleotide formyl-transferase [6]. The gene discussed is DHFR; the disease is mesothelioma.