Related Experiment Video
Updated: Jan 27, 2026
Culture of Bladder Cancer Organoids as Precision Medicine Tools
Published on: December 28, 2021
Targeting DNA Repair Defects for Precision Medicine in Prostate Cancer
Alejandro Athie1, Sara Arce-Gallego1, Macarena Gonzalez1,2
1Prostate Cancer Translational Research Group, Vall d'Hebron Institute of Oncology (VHIO), Cellex Center, Natzaret 115-117, 08035, Barcelona, Spain.
Purpose Of Review:
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.
Recent Findings:
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.
Insights
DNA repair gene defects are common in metastatic prostate cancer, offering new treatment targets. These include platinum chemotherapy, PARP inhibitors, and immune checkpoint inhibitors for personalized management.
Area of Science:
- Genomic medicine
- Oncology
- Molecular biology
Background:
- Genomic studies reveal frequent, actionable DNA repair gene alterations in localized and metastatic prostate cancer.
- Understanding these defects is crucial for advancing prostate cancer treatment strategies.
Purpose of the Study:
- To review current knowledge on DNA repair defects in prostate cancer.
- To outline how these genetic alterations can guide personalized prostate cancer management.
Main Methods:
- Literature review of genomic studies and clinical trials.
- Analysis of DNA repair gene mutations and their therapeutic implications.
Main Results:
- 20-25% of metastatic prostate cancers have DNA repair gene defects, primarily in homologous recombination genes.
- These defects sensitize tumors to platinum chemotherapy and PARP inhibitors.
- Combination therapies with androgen receptor-targeting agents show synergistic effects.
- Mismatch repair defects may identify patients benefiting from immune checkpoint inhibitors.
Conclusions:
- DNA damage repair pathways are clinically relevant targets for precision medicine in prostate cancer.
- Targeting DNA repair defects offers opportunities for personalized treatment strategies.
- Implications for family testing and early diagnosis due to inherited cancer risk.
Related Concept Videos
02:25Overview of DNA Repair
Chemically...
02:25Overview of DNA Repair
01:36Mismatch Repair
02:27Base-pairing and DNA Repair
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
01:54Base Excision Repair
The first step of...