oa Editorial [Hot topic: The Role of Pemetrexed in Lung Cancer (Guest Editors: Daoyuan Wang and Jianxing He)]

Despite significant advances in the treatment of non-small cell lung cancer (NSCLC) over the past several years, the prognosis for patients with advanced disease is still very poor. NSCLC patients treated with standard regimens containing cisplatin or carboplatin have a median survival of 8-11 months for patients with Stage IV disease and 5-7 months for patients with relapsed disease. Evaluation of new treatment strategies is ongoing to identify more effective treatment for patients with NSCLC. Pemetrexed, a pyrriol (2,3-d) pyrimidine antifolate is unique among the folate antagonists in that it is a powerful inhibitor of not only thymidylate synthase (TS) but also dihydrofolate reductase (DHFR) and the purine synthetic enzyme, glycinamide ribonucleotide formyltransferase (GARFT). It was approved for the treatment of mesothelioma and non-small cell lung cancer, currently being evaluated for the treatment of a variety of other solid tumors. Pemetrexed shows clear activity in non-small cell lung cancer. The first phase III study of pemetrexed in NSCLC established similar efficacy and a favorable safety profile for pemetrexed compared with docetaxel in the second-line setting. A second phase III study of pemetrexed in NSCLC reported noninferior efficacy and better tolerability for cisplatin plus pemetrexed than for cisplatin plus gemcitabine in the frontline setting. The knowledge of mechanisms of action of pemetrexed, and the understanding of the determinants of response, may allow the clinician to select patients who are more likely to respond to this drug, either used alone or in combination. This issue of Current Drug Targets tries to describe the pharmacology and mechanisms of action, clinical activity, predictive markers for hematological toxicity, and current status and future directions of the pemetrexed and the combination with platinums, gemcitabine, anti-angiogenic agents (bevacizumab and small molecule tyrosine kinase inhibitors), inhibitors of epidermal growth factor receptor (cetuximab and erlotinib), inhibitor of the protein kinase β (enzastaurin), and radiation therapy in patients with non-small cell lung cancer as well as lung adenocarcinoma, mixed subtype with bronchioloalveolar carcinoma features.