Docetaxel is the only globally approved first-line chemotherapy for the treatment of castrate resistant prostate cancer. Yhe universal truth is that all men taking docetaxel will become refractory to the treatment.
Zoledronic acid (ZA) is the most commonly used member of nitrogen-containing bisphosphonate family. By itself it has anti-tumor activity, including in prostate cancer.
In a study reported at the recent ASCO Annual Meeting it was shown that ZA pretreatment enhances the cytotoxic and apoptotic effect of docetaxel in docetaxel resistant (Doc-R) prostate cancer cells.
The researchers pretreated Doc-R prostate cancer cells with the increasing concentrations of ZA for 36 hours and with the increasing concentrations of docetaxel for additional 36 hours. Cell proliferation was then assessed.
It was found that the sequential treatment of 20 µM ZA followed by 10 nM docetaxel resulted in significantly enhanced cytotoxicity as compared to single agents alone in both at Doc-R prostate cancer cells. Moreover, docetaxel mediated DNA fragmentation and caspase 3/7 activity was increased by ZA pretreatment.
The research strongly suggest that pretreatment with ZA enhances docetaxel-induced cytotoxicity and apoptosis in Doc-R prostate cancer cells. These preliminary results make ZA a good candidate for overcoming docetaxel resistance in prostate cancer.
J Clin Oncol 32, 2014 (suppl; abstr e16105); Zeki Surmeli, Emir Bozkurt, Ozge Ozer, Harika Atmaca, Asli Kisim, Selim Uzunoglu, Ruchan Uslu, Burcak Karaca
Joel T. Nowak, M.A., M.S.W.