PARP Inhibitors in Ovarian & Breast Cancer

Treatments for ovarian and breast cancer have progressed over time, especially for patients with BRCA1 or BRCA2 mutations. A key advancement is the use of PARP inhibitors, which target how cancer cells repair their DNA and use this weakness to slow or stop tumour growth. The inhibitors block the PARP enzyme essential for the single-strand repair mechanism of the DNA. They are therapeutic due to their selective toxicity, particularly for cancers that alter another main DNA repair pathway, known as homologous recombination repair (HRR).

Evidence of Effectiveness

Strong clinical evidence supports the use of PARP inhibitors in BRCA-mutated and HRD-positive cancers. In ovarian cancer, maintenance therapies such as olaparib and niraparib have significantly improved progression-free survival after platinum-based chemotherapy. A 2024 systematic review of randomized controlled trials (5,815 patients) showed that PARP inhibitors significantly improve progression-free survival (PFS) in ovarian cancer.  In breast cancer, PARP inhibitors have shown strong benefits in HER2-negative, BRCA-mutated cases, especially in metastatic and early (adjuvant) treatment settings.

Their way of targeting the DNA repair pathways.

PARP inhibitors act by the process known as synthetic lethality. Cancer cells with BRCA1 or BRCA2 mutations cannot effectively repair double-strand DNA breaks through HRR. As a result, they rely heavily on PARP-mediated repair of single-strand breaks.

When PARP inhibitors block this pathway:

• Single-strand breaks accumulate
• These breaks convert into toxic double-strand breaks during replication
• The cancer cells, unable to repair them, undergo genomic instability and cell death

Some PARP drugs also “trap” PARP enzymes directly onto the DNA, creating additional damage and enhancing the treatment effect—while still sparing most healthy cells.

Eligibility & Practical Considerations

To determine whether a patient qualifies, clinicians usually test for:

• BRCA1/2 mutations
• HRD (homologous recombination deficiency) status

The most frequent side effects are fatigue, nausea, and blood-related problems such as anemia, thrombocytopenia, or neutropenia. Due to this, CBC checks, dose changes, or short treatment breaks are frequently needed.

Implications for Future Treatment

The introduction of PARP inhibitors has transformed ovarian and breast cancer therapy by directly addressing the vulnerabilities in DNA repair. They have been successful in providing effective, personalized therapy to a wide range of patients. Studies are currently underway to understand how all-in-one therapy can be used alongside other therapies to widen the effectiveness of PARP inhibitors to additional types of cancers.