Radiation therapy (RT) is commonly used for the treatment of localized prostate cancer (PCa). However, cancer cells often develop resistance to radiation through unknown mechanisms and pose an intractable challenge. Radiation resistance is highly unpredictable, rendering the treatment less effective in many patients and frequently causing metastasis and cancer recurrence. Understanding the molecular events that cause radioresistance in PCa will enable us to develop adjuvant treatments for enhancing the efficacy of RT. Radioresistant PCa depends on the elevated DNA repair system and the intracellular levels of reactive oxygen species (ROS) to proliferate, self-renew, and scavenge anti-cancer regimens, whereas the elevated heat shock protein 90 (HSP90) and the epithelial–mesenchymal transition (EMT) enable radioresistant PCa cells to metastasize after exposure to radiation. The up-regulation of the DNA repairing system, ROS, HSP90, and EMT effectors has been studied extensively, but not targeted by adjuvant therapy of radioresistant PCa. Here, we emphasize the effects of ionizing radiation and the mechanisms driving the emergence of radioresistant PCa. We also address the markers of radioresistance, the gene signatures for the predictive response to radiotherapy, and novel therapeutic platforms for targeting radioresistant PCa. This review provides significant insights into enhancing the current knowledge and the understanding toward optimization of these markers for the treatment of radioresistant PCa.
|Number of pages||29|
|Journal||Critical Reviews in Oncogenesis|
|State||Published - 2018|
Bibliographical noteFunding Information:
Research in the authors’ laboratory was supported in part by the National Institutes of Health (Grants CA188792 to L.C., CA205400-02 to D.S., and National Institute of General Medical Sciences COBRE Program P20 Grant GM121327 to L.C. and D.S.) and the James F. Hardymon Foundation (N.K.).
© 2018 Begell House, Inc.
- DNA repair
- Oxidative stress
- Prostate cancer
ASJC Scopus subject areas
- Cancer Research