Genomic studies of localized and metastatic prostate cancer have identified a high prevalence of clinically actionable alterations including mutations in DNA repair genes. In this manuscript, we review the current knowledge on DNA repair defects in prostate cancer and provide an overview of how these alterations can be targeted towards a personalized prostate cancer management.
Twenty to 25% of metastatic prostate cancers harbor defects in DNA repair genes, most commonly in the homologous recombination genes. These defects confer increased sensitivity to platinum chemotherapy or poly (ADP-ribose) polymerase (PARP) inhibitors. Recent trials also support a synergistic effect of combining these therapies with androgen receptor-targeting agents. Identification of mismatch-repair defects could result in defining a prostate cancer population who may benefit from immune checkpoint inhibitors. These data have implications for family testing and early diagnosis, as many of these mutations are linked to inherited risk of prostate cancer. The DNA damage repair pathways are clinically relevant in prostate cancer, being a target for precision medicine; combination with standard-of-care androgen receptor (AR)-targeting agents may be synergistic.
Current oncology reports. 2019 Mar 27*** epublish ***
Alejandro Athie, Sara Arce-Gallego, Macarena Gonzalez, Rafael Morales-Barrera, Cristina Suarez, Teresa Casals Galobart, Gonzalo Hernandez Viedma, Joan Carles, Joaquin Mateo
Prostate Cancer Translational Research Group, Vall d'Hebron Institute of Oncology (VHIO), Cellex Center, Natzaret 115-117, 08035, Barcelona, Spain., Prostate Cancer Translational Research Group, Vall d'Hebron Institute of Oncology (VHIO), Cellex Center, Natzaret 115-117, 08035, Barcelona, Spain. .