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Publication
Radiosensitization by enzalutamide for human prostate cancer is mediated through
the DNA damage repair pathway.
Authors Sekhar KR, Wang J, Freeman ML, Kirschner AN
Submitted By Submitted Externally on 12/17/2019
Status Published
Journal PLoS ONE
Year 2019
Date Published
Volume : Pages 14 : e0214670
PubMed Reference 30933998
Abstract Radiation therapy is often combined with androgen deprivation therapy in the
treatment of aggressive localized prostate cancer. However, castration-resistant
disease may not respond to testosterone deprivation approaches. Enzalutamide is
a second-generation anti-androgen with high affinity and activity that is used
for the treatment of metastatic disease. Although radiosensitization mechanisms
are known to be mediated through androgen receptor activity, this project aims
to uncover the detailed DNA damage repair factors influenced by enzalutamide
using multiple models of androgen-sensitive (LNCaP) and castration-resistant
human prostate cancer (22Rv1 and DU145). Enzalutamide is able to radiosensitize
both androgen-dependent and androgen-independent human prostate cancer models in
cell culture and xenografts in mice, as well as a treatment-resistant
patient-derived xenograft. The enzalutamide-mediated mechanism of
radiosensitization includes delay of DNA repair through temporal prolongation of
the repair factor complexes and halting the cell cycle, which results in
decreased colony survival. Altogether, these findings support the use of
enzalutamide concurrently with radiotherapy to enhance the treatment efficacy
for prostate cancer.




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