The applications of the novel polymeric fluoropyrimidine F10 in cancer treatment: current evidence.
F10 is a novel polymeric fluoropyrimidine drug candidate with strong anticancer activity in multiple preclinical models. F10 has strong potential for impacting cancer treatment because it displays high cytotoxicity toward proliferating malignant cells with minimal systemic toxicities thus providing an improved therapeutic window relative to traditional fluoropyrimidine drugs, such as 5-fluorouracil. F10 has a unique mechanism that involves dual targeting of thymidylate synthase and Top1. In this review, the authors provide an overview of the studies that revealed the novel aspects of F10's cytotoxic mechanism and summarize results obtained in preclinical models of acute myeloid leukemia, acute lymphocytic leukemia, glioblastoma and prostate cancer that demonstrate the strong potential of F10 to improve treatment outcomes.
Wake Forest Baptist Medical Center Comprehensive Cancer Center, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.|Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
William H
WH
Gmeiner
Wake Forest Baptist Medical Center Comprehensive Cancer Center, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.|Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.|Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
Waldemar
W
Debinski
Wake Forest Baptist Medical Center Comprehensive Cancer Center, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.|Department of Neurobiology & Anatomy, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
Carol
C
Milligan
Wake Forest Baptist Medical Center Comprehensive Cancer Center, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.|Department of Pathology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
David
D
Caudell
Wake Forest Baptist Medical Center Comprehensive Cancer Center, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.|Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.|Department of Hematology/Oncology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
Timothy S
TS
Pardee
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D005468:Fluorodeoxyuridylate / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*
D000970:Antineoplastic Agents; C435305:FdUMP(10); D005468:Fluorodeoxyuridylate
acute leukemia; cancer chemotherapy; fluoropyrimidine; glioblastoma; prostate cancer; thymineless death; topoisomerase