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Critical Reviews™ in Oncogenesis
SJR: 0.631 SNIP: 0.503 CiteScore™: 2

ISSN Print: 0893-9675
ISSN Online: 2162-6448

Critical Reviews™ in Oncogenesis

DOI: 10.1615/CritRevOncog.2018025946
pages 39-67

Profiles of Radioresistance Mechanisms in Prostate Cancer

Luksana Chaiswing
Department of Toxicology and Cancer Biology, University of Kentucky, Lexington, Kentucky
Heidi L. Weiss
The Markey Biostatistics and Bioinformatics Shared Resource Facility, University of Kentucky, Lexington, Kentucky
Rani D. Jayswal
The Markey Biostatistics and Bioinformatics Shared Resource Facility, University of Kentucky, Lexington, Kentucky
Daret K. St. Clair
Department of Toxicology and Cancer Biology, University of Kentucky, Lexington, Kentucky
Natasha Kyprianou
Department of Toxicology and Cancer Biology, Department of Urology, Department of Biochemistry, University of Kentucky, Lexington, Kentucky

ABSTRACT

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.


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