Folate-targeted therapeutic and imaging agents for cancer.
Cancer therapies that exploit targeting ligands to deliver attached cytotoxic drugs selectively to malignant cells are currently receiving significant attention. While antibody-targeted drugs have been the first to enter the clinic, recent studies demonstrate that the vitamin folic acid can also be used to deliver attached imaging and therapeutic agents selectively to malignant cells in both animal tumor models and human cancer patients. Thus, folate conjugates bind to folate receptors that are overexpressed on approximately 40% of human cancers and mediate internalization of their attached drugs by receptor-mediated endocytosis. With the use of proper linkers, folate-targeted drugs can be released inside their target cells where they can perform their desired cytotoxic functions. Based on this strategy, six folate-targeted drugs are currently in human clinical trials.
Department of Chemistry, 560 Oval Drive, Purdue University, West Lafayette, IN 47907, USA. plow@purdue.edu
Philip Stewart
PS
Low
Sumith Anurasiri
SA
Kularatne
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002352:Carrier Proteins / Q000096:biosynthesis / Q000378:metabolism; D003952:Diagnostic Imaging / Q000379:methods*; D016503:Drug Delivery Systems / Q000379:methods*; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000008:administration & dosage* / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000378:metabolism
D000970:Antineoplastic Agents; D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; D011956:Receptors, Cell Surface; D005492:Folic Acid