Molecular mechanism implicated in Pemetrexed-induced apoptosis in human melanoma cells

Aitziber Buqué, Jangi Sh Muhialdin, Alberto Muñoz, Begoña Calvo, Sergio Carrera, Unai Aresti, Aintzane Sancho, Itziar Rubio, Guillermo López-Vivanco

Metastatic melanoma is a lethal skin cancer and its incidence is rising every year. It represents a challenge for oncologist, as the current treatment options are non-curative in the majority of cases; therefore, the effort to find and/or develop novel compounds is mandatory. Pemetrexed (Alimta®, MTA) is a multitarget antifolate that inhibits folate-dependent enzymes: thymidylate synthase, dihydrofolate reductase and glycinamide ribonucleotide formyltransferase, required for de novo synthesis of nucleotides for DNA replication. It is currently used in the treatment of mesothelioma and non-small cell lung cancer (NSCLC), and has shown clinical activity in other tumors such as breast, colorectal, bladder, cervical, gastric and pancreatic cancer. However, its effect in human melanoma has not been studied yet.