Scagliotti Giorgio V, Ceppi Paolo, Capelletto Enrica, Novello Silvia
Department of Clinical and Biological Sciences, University of Torino, Torino, Italy.
Clin Lung Cancer. 2009 Mar;10 Suppl 1:S35-40. doi: 10.3816/CLC.2009.s.006.
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.
培美曲塞是一种第三代抗叶酸药物，已被批准与顺铂联合用于恶性胸膜间皮瘤的全身治疗，作为单药用于非小细胞肺癌的二线治疗。2008年，欧洲药品管理局（EMEA）和美国食品药品监督管理局（FDA）均批准其用于基于组织学的一线治疗。培美曲塞的主要分子靶点胸苷酸合成酶在鳞状细胞癌和小细胞肺癌中的mRNA和蛋白质表达高于腺癌。这种差异表达很可能从分子水平解释了培美曲塞在肺癌各种组织学类型中的临床活性差异，包括在小细胞肺癌中的边缘活性。这些产生假设的发现目前正在前瞻性研究中得到验证。
