Radiation- and photo-induced activation of 5-fluorouracil prodrugs as a strategy for the selective treatment of solid tumors.
5-Fluorouracil (5-FU) is used widely as an anticancer drug to treat solid cancers, such as colon, breast, rectal, and pancreatic cancers, although its clinical application is limited because 5-FU has gastrointestinal and hematological toxicity. Many groups are searching for prodrugs with functions that are tumor selective in their delivery and can be activated to improve the clinical utility of 5-FU as an important cancer chemotherapeutic agent. UV and ionizing radiation can cause chemical reactions in a localized area of the body, and these have been applied in the development of site-specific drug activation and sensitization. In this review, we describe recent progress in the development of novel 5-FU prodrugs that are activated site specifically by UV light and ionizing radiation in the tumor microenvironment. We also discuss the chemical mechanisms underlying this activation.
Ito
Takeo
T
Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto University, Kyoto 615-8510, Japan.
Tanabe
Kazuhito
K
Yamada
Hisatsugu
H
Hatta
Hiroshi
H
Nishimoto
Sei-ichi
S
D016503:Drug Delivery Systems / Q000379:methods*; D005472:Fluorouracil / Q000008:administration & dosage*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D011355:Prodrugs / Q000528:radiation effects*; D011839:Radiation, Ionizing; D014466:Ultraviolet Rays
D011355:Prodrugs; D005472:Fluorouracil