Clinical and preclinical studies have revealed that alterations in DNA damage response (DDR) pathways may play an important role in prostate cancer (PCa) etiology and progression. These alterations can influence PCa responses to radiotherapy and anti-androgen treatment. The identification of DNA repair gene aberrations in PCa has driven the interest for further evaluation whether these genetic changes may serve as biomarkers for patient stratification.

In this review, we summarize the current knowledge on DDR alterations in PCa, their potential impact on clinical interventions and prospects for improved management of PCa. We particularly focus on the influence of DDR gene mutations on PCa initiation and progression and describe the underlying mechanisms.

A better understanding of these mechanisms, will contribute to better disease management as treatment strategies can be chosen based on the specific disease properties, since a growing number of treatments are targeting DDR pathway alterations (such as Poly(ADP-ribose) polymerase inhibitors). Furthermore, the recently discovered crosstalk between the DDR and androgen receptor signaling opens a new array of possible strategies to optimize treatment combinations. We discuss how these recent and ongoing studies will help to improve diagnostic, prognostic and therapeutic approaches for PCa management.

Prostate cancer and prostatic diseases. 2019 Jun 13 [Epub ahead of print]

Wenhao Zhang, Dik C van Gent, Luca Incrocci, Wytske M van Weerden, Julie Nonnekens

Department of Molecular Genetics, Erasmus MC, Rotterdam, The Netherlands., Department of Radiation Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., Department of Experimental Urology, Erasmus MC, Rotterdam, The Netherlands., Department of Molecular Genetics, Erasmus MC, Rotterdam, The Netherlands. .