What Are PARP Inhibitors?

PARP inhibitors (PARPi) are a class of targeted oncology drugs that have transformed treatment — particularly for ovarian, breast, prostate, and pancreatic cancers with specific DNA repair gene mutations. They work by blocking an enzyme called PARP (Poly ADP-Ribose Polymerase), which cancer cells rely on to repair their DNA. By inhibiting this repair mechanism, these drugs cause cancer cells to accumulate so much DNA damage that they die.

The Science: Synthetic Lethality

The power of PARP inhibitors is rooted in a concept called synthetic lethality. Normally, cells have multiple DNA repair pathways as backup systems. Patients with mutations in BRCA1 or BRCA2 genes already have a compromised form of DNA repair called homologous recombination repair (HRR). When a PARP inhibitor blocks a second, independent repair pathway, cancer cells — already hobbled by their BRCA mutation — have no way to fix their DNA damage and die. Healthy cells with intact BRCA genes can use their backup repair pathways and largely survive.

FDA-Approved PARP Inhibitors

Drug (Generic) Brand Name Approved Cancer Types
Olaparib Lynparza Ovarian, breast, pancreatic, prostate (BRCA-mutated)
Rucaparib Rubraca Ovarian, fallopian tube, peritoneal (BRCA-mutated)
Niraparib Zejula Ovarian, fallopian tube, peritoneal (maintenance)
Talazoparib Talzenna HER2-negative, locally advanced/metastatic breast cancer (BRCA-mutated)

Who Is Eligible for PARP Inhibitor Therapy?

Eligibility is largely determined by genetic testing. Patients are typically candidates if they have:

  • A confirmed BRCA1 or BRCA2 mutation (germline or somatic)
  • Other homologous recombination deficiency (HRD) mutations (depending on the drug and indication)
  • Met specific criteria regarding prior treatment lines and cancer stage

Genetic testing — both germline (inherited) and somatic (tumor-based) — is essential before starting therapy. Your oncologist may order a panel test that looks at multiple HRR-related genes simultaneously.

How Are PARP Inhibitors Taken?

Most PARP inhibitors are taken as oral capsules or tablets, typically once or twice daily at home. This makes them more convenient than IV chemotherapy for many patients. Treatment continues until disease progression or unacceptable toxicity.

Common Side Effects

PARP inhibitors are generally better tolerated than traditional chemotherapy, but side effects still occur:

  • Nausea and vomiting — most common, often manageable with anti-nausea medications
  • Fatigue
  • Anemia (low red blood cell count) — may require dose adjustments or transfusions
  • Thrombocytopenia (low platelets)
  • Rare but serious: Myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) with long-term use

Resistance to PARP Inhibitors

As with many targeted therapies, resistance can develop over time. Research into overcoming PARP inhibitor resistance — including combination strategies with immunotherapy or other targeted agents — is an active area of clinical investigation.

Speak with your oncologist about whether PARP inhibitor therapy is appropriate for your specific diagnosis and mutation profile.