title: Pralatrexate pharmacology and clinical development.
abstract: Folates are well known to be essential for many cellular processes, including cellular proliferation. As a consequence, antifolates, the fraudulent mimics of folic acid, have been shown to be potent therapeutic agents in many cancers. Over the past several decades, efforts to improve on this class of drugs have met with little success. Recently, one analog specifically designed to have high affinity for the reduced folate carrier, which efficiently internalizes natural folates and antifolates, has been shown to be very active in T-cell lymphoma. Pralatrexate, approved by the U.S. Food and Drug Administration in 2009, is highly active across many lymphoid malignancies, including chemotherapy-resistant T-cell lymphoma. Emerging combination studies have now shown that pralatrexate is highly synergistic with gemcitabine, histone deacetylase inhibitors like romidepsin and bortezomib. These insights are leading to a number of novel phase I and II combination studies which could challenge existing regimens like CHOP, and improve the outcome of patients with T-cell lymphoma.
authors: Authors' Affiliations: Department of Medicine, Center for Lymphoid Malignancies, Columbia University Medical Center; and Tisch Cancer Institute, Mount Sinai School of Medicine, New York, New York.
authors: Enrica
authors: E
authors: Marchi
authors: Michael
authors: M
authors: Mangone
authors: Kelly
authors: K
authors: Zullo
authors: Owen A
authors: OA
authors: O'Connor
mesh_terms: D000630:Aminopterin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D001897:Boronic Acids / Q000008:administration & dosage*; D000069286:Bortezomib; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D047630:Depsipeptides / Q000008:administration & dosage; D018572:Disease-Free Survival; D017277:Drug Approval; D004357:Drug Synergism; D006801:Humans; D016399:Lymphoma, T-Cell / Q000188:drug therapy*; D008297:Male; D011719:Pyrazines / Q000008:administration & dosage*; D016896:Treatment Outcome; D014481:United States; D014486:United States Food and Drug Administration; D000093542:Gemcitabine
chemical_list: C418863:10-propargyl-10-deazaaminopterin; D001897:Boronic Acids; D047630:Depsipeptides; D011719:Pyrazines; D003841:Deoxycytidine; D000069286:Bortezomib; C087123:romidepsin; D000630:Aminopterin; D000093542:Gemcitabine