Antimetabolites and cancer: emerging data with a focus on antifolates.

Antimetabolites, especially antifolates, play an important role in the treatment of a variety of both malignant, and non-malignant diseases, such as rheumatoid arthritis, and bacterial and parasitic infections. Recently, new antimetabolites have become an area for anticancer drug expansion. Gemcitabine has emerged as an important new agent in several tumour types, including non-small cell lung cancer, pancreatic, bladder, breast and ovarian cancers. Capecitabine is an intriguing new prodrug, offering tumour selectivity and prolonged tumour exposure to 5-FU. More potent thymidylate synthase inhibitors have also been developed; raltitrexed and pemetrexed are now commercially available for the treatment of mesothelioma, non-small cell lung cancer and other solid cancer types. This review will describe the most recent findings and their potential clinical applications.