PARP inhibitors

What it is

PARP inhibitors are targeted cancer drugs that block DNA repair; olaparib was first FDA-approved in 2014. They inhibit poly(ADP-ribose) polymerase enzymes, mainly PARP1 and PARP2, which help cells repair single-strand DNA breaks. The most important practical point is that these drugs work best in tumours with defective homologous recombination repair, especially cancers with BRCA1 or BRCA2 mutations or other homologous recombination repair gene abnormalities.

PARP inhibitors are used in selected patients with ovarian, breast, prostate, and pancreatic cancers, and sometimes in other settings through clinical trials. Common drugs in this class include:

Drug	Typical status/use area
Olaparib	Ovarian, breast, pancreatic, prostate cancers
Niraparib	Ovarian cancer; studied in prostate and other cancers
Rucaparib	Ovarian and prostate cancers; studied in pancreatic cancer
Talazoparib	Breast and prostate cancers
Veliparib	Investigational in many cancers; not widely approved as routine therapy

In India, access depends on the exact cancer type, biomarker result, prior treatment, and local regulatory or institutional availability. For many patients, treatment decisions are linked to tumour testing for BRCA1/2 and sometimes broader homologous recombination repair genes.

How it works

PARP enzymes detect and help repair single-strand DNA damage. When a PARP inhibitor blocks this process, single-strand breaks can persist and convert into more dangerous double-strand breaks during DNA replication. Normal cells may still repair some of this damage through homologous recombination. But cancer cells with homologous recombination deficiency, such as those with BRCA1 or BRCA2 loss, are much less able to recover.

This creates a treatment strategy called synthetic lethality. A tumour cell may survive with one repair pathway broken, but if PARP is also blocked, DNA damage accumulates until the cell dies. Some PARP inhibitors also "trap" PARP on DNA, which can increase anticancer activity.

This is why PARP inhibitors are often described as biomarker-guided therapy. A BRCA mutation does not guarantee benefit in every case, and some patients without BRCA mutations can still respond, especially if the tumour shows broader homologous recombination deficiency.

Evidence and uses

The strongest evidence is in ovarian cancer, where PARP inhibitors are used as maintenance therapy after response to platinum-based chemotherapy and, in some settings, as treatment for recurrent disease. A Cochrane review and ASCO guidance support their role in selected ovarian cancer settings, especially when BRCA mutation or homologous recombination deficiency is present.

Examples from major trials include:

1. Olaparib in recurrent ovarian cancer: a phase 2 trial reported median progression-free survival of 13.6 months versus 7.2 months with placebo in platinum-sensitive recurrent serous ovarian cancer.
2. Niraparib in recurrent ovarian cancer: the ENGOT-OV16/NOVA trial reported median progression-free survival of 21.0 months in the germline BRCA-mutated cohort.
3. Olaparib in metastatic HER2-negative breast cancer with germline BRCA mutation: the OlympiAD trial reported median progression-free survival of 7.0 months versus 4.2 months with standard therapy.
4. Olaparib in metastatic castration-resistant prostate cancer: benefit has been shown in selected men with BRCA1/2 or other homologous recombination repair gene alterations.
5. Maintenance olaparib in metastatic pancreatic cancer with germline BRCA mutation: trials showed longer progression-free survival in selected patients whose disease had not progressed on platinum chemotherapy.

PARP inhibitors are also being studied in combinations with chemotherapy, anti-angiogenic drugs, immunotherapy, and radiotherapy. Some combinations are promising, but toxicity can increase, especially bone marrow suppression.

A key limitation is that benefit varies by tumour type and biomarker. For example, not all homologous recombination repair gene changes predict the same level of response. Evidence in lung cancer, liver cancer, melanoma, and several other tumours is still mixed or early, and many uses remain investigational.

Safety and interactions

PARP inhibitors can cause important side effects and need regular monitoring. The most common problems are:

Common adverse effect	Why it matters
Anaemia	May cause fatigue, breathlessness, need for dose changes or transfusion
Neutropenia	Raises infection risk
Thrombocytopenia	Raises bruising and bleeding risk
Nausea or vomiting	May affect eating and adherence
Fatigue	Common and sometimes persistent
Changes in liver or kidney tests	May require monitoring and dose adjustment

Less common but serious risks include myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML), which have been reported with PARP inhibitors, especially after prior chemotherapy exposure. These events are uncommon but clinically important.

Drug interactions differ by agent. Some PARP inhibitors are affected by liver enzymes and transport proteins, so other prescription drugs, antifungals, antibiotics, seizure medicines, and herbal products may change drug levels. Because many cancer patients in India also use over-the-counter medicines or traditional products, it is important to tell the oncology team about all tablets, syrups, supplements, and herbal preparations.

Patients on PARP inhibitors usually need periodic complete blood counts and chemistry tests. Do not start, stop, or combine these medicines without oncology guidance.

When to see a clinician

Contact your cancer team promptly if you develop fever, chills, unusual bruising, bleeding gums, black stools, severe tiredness, worsening shortness of breath, chest pain, persistent vomiting, or inability to eat or drink. These can signal infection, severe anaemia, low platelets, dehydration, or other complications.

You should also ask your clinician whether genetic or tumour testing is appropriate before starting therapy. For many patients, the decision to use a PARP inhibitor depends on results for germline or somatic BRCA1/2 and sometimes a broader homologous recombination repair panel.

If you are being treated in India, ask whether the drug is being used as standard care, maintenance therapy, or through a clinical trial, and what monitoring schedule is planned.

Limitations and open questions

PARP inhibitors are not suitable for every cancer patient, and they are not interchangeable across all tumour types. The best-established uses are in selected ovarian, breast, prostate, and pancreatic cancers, but the exact indication depends on prior treatment, biomarker status, and the specific drug.

Resistance can develop. Tumours may regain DNA repair ability through secondary mutations or other escape mechanisms, which can make the drug stop working over time. Researchers are studying whether markers such as broader homologous recombination deficiency scores, BRCA1 methylation patterns, or proteins like SLFN11 can better predict benefit.

Evidence for combining PARP inhibitors with immunotherapy or radiotherapy is still evolving. Some preclinical and early clinical studies are encouraging, but stronger comparative trials are still needed. For patients and families, the main takeaway is that PARP inhibitors can be highly useful in the right biomarker-defined setting, but they require careful selection, monitoring, and discussion with an oncologist.