Drivers of Radioresistance in Prostate Cancer

Prostate cancer (PCa) is the second most commonly diagnosed cancer worldwide. Radiotherapy remains one of the first-line treatments in localised disease and may be used as monotherapy or in combination with other treatments such as androgen deprivation therapy or radical prostatectomy. Despite advancements in delivery methods and techniques, radiotherapy has been unable to totally overcome radioresistance resulting in treatment failure or recurrence of previously treated PCa. Various factors have been linked to the development of tumour radioresistance including abnormal tumour vasculature, oxygen depletion, glucose and energy deprivation, changes in gene expression and proteome alterations. Understanding the biological mechanisms behind radioresistance is essential in the development of therapies that are able to produce both initial and sustained response to radiotherapy. This review will investigate the different biological mechanisms utilised by PCa tumours to drive radioresistance.