Updated clinical information on multitargeted antifolates in lung cancer.
Pemetrexed, a third-generation antifolate already indicated in combination with cisplatin for the systemic treatment of malignant pleural mesothelioma and, as a single agent, for the second-line treatment of non-small-cell lung cancer was in 2008 granted approval for histologically based first-line treatment by both the EMEA and FDA. Thymidylate synthase, the main molecular target of pemetrexed, has higher mRNA and protein expression in squamous- and small-cell lung cancer compared with adenocarcinoma. This differential expression might well molecularly explain the differential clinical activity of pemetrexed in the various histotypes of lung cancer, including the marginal activity in small-cell lung cancer. These hypothesis-generating findings are currently validated in prospective studies.
Scagliotti
Giorgio V
GV
Department of Clinical and Biological Sciences, University of Torino, Torino, Italy. giorgio.scagliotti@unito.it
Ceppi
Paolo
P
Capelletto
Enrica
E
Novello
Silvia
S
D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D002986:Clinical Trials as Topic; D005493:Folic Acid Antagonists / Q000627:therapeutic use*; D017353:Gene Deletion; D005971:Glutamates / Q000627:therapeutic use; D006147:Guanine / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D000068437:Pemetrexed; D011683:Purine-Nucleoside Phosphorylase / Q000037:antagonists & inhibitors / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy; D013940:Thymidylate Synthase / Q000235:genetics
D005493:Folic Acid Antagonists; D005971:Glutamates; D012333:RNA, Messenger; D000068437:Pemetrexed; D006147:Guanine; D013940:Thymidylate Synthase; D011683:Purine-Nucleoside Phosphorylase; C021784:5'-methylthioadenosine phosphorylase