Therapeutic value of quinazoline-based compounds in prostate cancer.
Certain α1-adrenoreceptor antagonists induce significant apoptosis and impair tumor vascularity without affecting cellular proliferation, effects specific to the quinazoline structure. These anticancer effects have been attributed to both induction of classical apoptosis and reversal of anoikis resistance via disruption of integrin-mediated cell survival pathways. Recent drug optimization efforts have generated several novel compounds with quinazoline-derived chemical structure that exert potent anti-tumor activity via anoikis. Results from pre-clinical and clinical studies implicate a potential value of quinazoline-based analogues in prostate cancer prevention and therapy. A retrospective study of a large patient cohort at our center, revealed that treatment with α1-andrenoreceptor antagonists significantly reduced the risk of developing prostate cancer, indicating a potential chemopreventative mechanism for these FDA-approved agents. In the present review we discuss the current understanding of the signaling mechanisms reversing anoikis resistance by the quinazoline-based compounds in prostate tumors, towards enabling identification of novel therapeutic targets for the treatment of metastatic castration-resistant prostate cancer (CRPC).
Combs Res. Bldg., Rm. 306, University of Kentucky Medical Center, Lexington, KY 40536, U.S.A. nkypr2@uky.edu.
Johnathan
J
Bilbro
Matthew
M
Mart
Natasha
N
Kyprianou
D000818:Animals; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D011799:Quinazolines / Q000737:chemistry* / Q000627:therapeutic use*
D011799:Quinazolines
DZ-50; Quinazoline; anoikis; doxazosin; prostate cancer; review; terazosin; vascularity