Evaluation of the radiosensitizing potency of chemotherapeutic agents in prostate cancer cells

Rae, C. and Mairs, R. J. (2017) Evaluation of the radiosensitizing potency of chemotherapeutic agents in prostate cancer cells. International Journal of Radiation Biology, 93(2), pp. 194-203. (doi: 10.1080/09553002.2017.1231946) (PMID:27600766)

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Abstract

PURPOSE: Despite recent advances in the treatment of metastatic prostate cancer, survival rates are low and treatment options are limited to chemotherapy and hormonal therapy. Although ionizing radiation is used to treat localized and metastatic prostate cancer, the most efficient use of radiotherapy is yet to be defined. Our purpose was to determine in vitro the potential benefit to be gained by combining radiation treatment with cytotoxic drugs. MATERIALS AND METHODS: Inhibitors of DNA repair and heat shock protein 90 and an inducer of oxidative stress were evaluated in combination with x-radiation for their capacity to reduce clonogenic survival and delay the growth of multicellular tumor spheroids. RESULTS: Inhibitors of the PARP DNA repair pathway, olaparib and rucaparib, and the HSP90 inhibitor 17-DMAG, enhanced the clonogenic cell kill and spheroid growth delay induced by x-radiation. However, the oxidative stress-inducing drug elesclomol failed to potentiate the effects of x-radiation. PARP inhibitors arrested cells in the G2/M phase when administered as single agents or in combination with radiation, whereas elesclomol and 17-DMAG did not affect radiation-induced cell cycle modulation. CONCLUSIONS: These results indicate that radiotherapy of prostate cancer may be optimized by combination with inhibitors of PARP or HSP90, but not elesclomol.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Mairs, Professor Robert and Rae, Dr Colin
Authors: Rae, C., and Mairs, R. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Research Group:Radiation Oncology
Journal Name:International Journal of Radiation Biology
Journal Abbr.:Int J Radiat Biol.
Publisher:Taylor & Francis
ISSN:0955-3002
ISSN (Online):1362-3095
Published Online:06 September 2016
Copyright Holders:Copyright © 2016 The Authors
First Published:First published in International Journal of Radiation Biology 93(2):194-203
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
609641Enhancement of prostate targeted radiotherapy using PSMA-seeking agents in combination with radiosensitizers.Robert MairsThe Prostate Cancer Charity (PROST-CHAR)PG12-12ICS - EPIGENETICS