title: TAS-102 an Emerging Oral Fluoropyrimidine.
abstract: Colon cancer is a common type of cancer with high mortality. The standard therapy for colon cancer is 5-FU-based regimen, although the current response rate to 5-FU is only 10-15%. Various approaches have been used to improve the efficacy of 5-FU including inhibition of its degradation enzyme dihydropyrimidine dehydrogenase (DPD) such as S1, UTF, use of 5-FU pro-drug capecitabine to exploit thymidine phosphorylase (TP) and supplementation of reduced folate acid to increase cytotoxicity. TAS-102 is a newly-developed anti-folate drug containing the 5-FU analogue trifluridine (TFD) and tipiracil hydrochloride (TPI). TPI is an inhibitor of TFD degradation enzyme thymidine phosphorylase and thus increases the bioavailability of TFD. In the present review, we summarize recent progress with regard to TAS-102, including pre-clinical tests and clinical trials. We further propose several approaches to further improve the efficacy of TAS-102 including combination with targeted therapy and immune therapy.
authors.affiliation: School of Biomedical Sciences, University of Queensland, St. Lucia, Australia.
authors.forename: Jiezhong
authors.initials: J
authors.lastname: Chen
authors.affiliation: Illawarra Health and Medical Research Institute, The University of Wollongong, Wollongong, Australia.
authors.forename: Mei
authors.initials: M
authors.lastname: Han
authors.affiliation: Department of Medicine and Cancer Center, Tufts Medical Center, Tufts University School of Medicine, Boston, MA, U.S.A. wsaif@tuftsmedicalcenter.org.
authors.forename: Muhammad Wasif
authors.initials: MW
authors.lastname: Saif
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D004338:Drug Combinations; D005493:Folic Acid Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007167:Immunotherapy; D058990:Molecular Targeted Therapy; D011759:Pyrrolidines; D013941:Thymine; D016896:Treatment Outcome; D014271:Trifluridine / Q000008:administration & dosage* / Q000009:adverse effects; D014498:Uracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*
chemical_list: D000970:Antineoplastic Agents; D004338:Drug Combinations; D005493:Folic Acid Antagonists; D011759:Pyrrolidines; C000613803:trifluridine tipiracil drug combination; D014498:Uracil; D013941:Thymine; D014271:Trifluridine
keywords: Drug resistance; apoptosis; combination therapy; review; survival signaling