What Are PARP Inhibitors?
PARP inhibitors (often called PARPi) are cancer medicines you take as pills. PARP is a protein your cells use to fix small breaks in their DNA. PARP inhibitors block this repair process. When cancer cells can’t fix their DNA damage, they may stop growing or die.
PARP inhibitors studied and used in prostate cancer include saruparib, olaparib, rucaparib, niraparib, and talazoparib.
Why Do Genes Matter?
Some prostate cancers already have trouble repairing DNA. This happens because of changes (called mutations) in certain genes that normally help fix DNA damage. A key group of these genes is called HRR genes (short for homologous recombination repair).
The most well-known HRR genes are BRCA1 and BRCA2, but others include PALB2, ATM, CDK12, and CHEK2.
In studies of advanced prostate cancer, about 1 in 4 men (25–30%) had either an inherited mutation or a mutation in the tumor itself that affects DNA repair. Cancers with HRR mutations—especially BRCA2—are more likely to respond to PARP inhibitors.
Who Is Most Likely to Benefit?
PARP inhibitors work best when your cancer has certain HRR gene mutations.
Most benefit seen in: BRCA1 and BRCA2 (especially BRCA2), PALB2
Smaller or less consistent benefit: ATM, CHEK2, and CDK12 (many men with these changes do not respond)
Because response depends on your genes, testing is important.
Your care team may recommend:
- Germline testing (blood or saliva) to look for inherited mutations
- Tumor testing (from a biopsy or surgery sample)
- Liquid biopsy (a blood test that looks for tumor DNA)
If an inherited mutation is found, your doctor may suggest genetic counseling, which can also help guide care for family members.
When Are PARP Inhibitors Used?
Most research and current use is in metastatic castration-resistant prostate cancer (mCRPC). Metastatic means the cancer has spread. Castration-resistant means it is growing despite very low testosterone levels from hormone therapy.
1. PARP inhibitors used alone
PARP inhibitors can control cancer well in men with BRCA1/2 or PALB2 mutations. For other genetic changes, the benefits are often limited.
2. PARP inhibitors combined with hormone-based medicines
PARP inhibitors may be used with hormone-blocking medicines, such as Abiraterone (usually with prednisone) and Enzalutamide.
The goal is to attack the cancer in two ways at once. Large studies show some combinations can delay cancer growth and, in certain groups, mainly those with HRR-positive or BRCA-mutated cancers, improve overall survival.
3. Earlier-stage prostate cancer (mostly clinical trials)
PARP inhibitors are still being studied in earlier settings, including:
- Metastatic hormone-sensitive prostate cancer (mHSPC)
- High-risk cancer before surgery
- After surgery or radiation
- Rising PSA after local treatment
Many of these uses are promising but still under investigation.
What Benefits Can You Expect?
Benefits depend on your gene results and overall treatment plan. Possible benefits include:
- More time before the cancer grows or spreads
- Tumor shrinkage in some men (more common with BRCA1/2 or PALB2)
- Delaying the need for chemotherapy
- Longer overall survival in some groups
It’s important to know that not everyone responds, and even cancers that respond at first may become resistant over time.
Practical Tips
- Take your medicine exactly as prescribed
- Keep an up-to-date list of all medications and supplements
- Report side effects early — many can be managed with dose changes or supportive care
- Ask about cost, insurance coverage, and patient support programs
Questions to Ask Your Care Team
- Do I have an HRR or BRCA mutation? Is it inherited in the tumor or both?
- Is a PARP inhibitor right for me alone or in combination?
- What benefits are realistic for me?
- What lab tests and visits will I need?
- What side effects should prompt an urgent call?
- Are there clinical trials that match my cancer stage and gene results?
Key Takeaways
- PARP inhibitors are targeted pills that work best when prostate cancer has trouble repairing DNA
- The strongest evidence of benefit is in BRCA1/2 (especially BRCA2) and PALB2 mutations
- Combining PARP inhibitors with hormone therapy may help more men with HRR-positive disease
- Blood and tumor testing help guide treatment decisions
- Regular monitoring and early reporting of side effects improve safety
This information is for education only and does not replace advice from your oncology care team.
