What is a PARP Inhibitor and How Does It Treat Ovarian Cancer?

Ovarian cancer is a complex and challenging disease, but recent advancements in targeted therapies like PARP inhibitors are providing new hope for patients. 

PARP inhibitors are an exciting class of drugs that have shown promising results in treating ovarian cancers, particularly those associated with BRCA gene mutations. In this article, we’ll dive into what PARP inhibitors are, how they work, and what ovarian cancer patients can expect from this innovative treatment option. While PARP inhibitors are also used to treat certain breast, prostate, and pancreatic cancers, our focus will be on their application in ovarian cancer.

What is a PARP Inhibitor?

To understand PARP inhibitors, let’s start with the basics. PARP, which stands for poly adenosine diphosphate-ribose polymerase, is a protein that helps cells repair damage to their DNA.

DNA damage is a normal occurrence in cells, but when left unrepaired, it can lead to the development of cancer. In some types of cancer cells, including ovarian cancer cells, PARP plays a crucial role in repairing DNA damage through a process called homologous recombination repair (HRR).

PARP inhibitors block the activity of PARP enzymes, preventing them from repairing damaged DNA in cancer cells. By disrupting this repair mechanism, PARP inhibitors aim to cause the cancer cells to accumulate so much DNA damage that they ultimately die.

How Do PARP Inhibitors Work?

PARP inhibitors work particularly well against cancer cells that already have difficulty repairing their DNA due to gene mutations like BRCA1 or BRCA2. (You can learn more about BRCA testing for ovarian cancer and what your results mean.) This is because of a concept called “synthetic lethality.”

So, how do PARP inhibitors act on cancerous cells? Imagine a car with two sets of brakes: regular and emergency. If the regular brakes fail, the car can still stop safely using the emergency brakes. But if both sets of brakes fail simultaneously, the car won’t be able to stop at all.

Similarly, cancer cells with BRCA1 or BRCA2 mutations have a faulty “set of brakes” for repairing their DNA. They rely on PARP, which acts as their “emergency brakes,” to fix DNA damage. When a PARP inhibitor is used, it disables the emergency brakes. The cancer cells are left unable to repair their DNA effectively, causing them to accumulate damage and eventually die.

So, the combination of two problems (the BRCA1 or BRCA2 mutation and the PARP inhibitor) makes the treatment effective. This is synthetic lethality: the cancer cells can survive with either problem alone, but when both issues occur together, it leads to their death.

In normal cells that don’t have BRCA1 or BRCA2 mutations, the “regular brakes” for DNA repair still work, even when PARP is inhibited. This means that PARP inhibitors are less likely to harm healthy cells, making them a targeted therapy for cancers with these specific mutations.

When are PARP Inhibitors Used to Treat Ovarian Cancer?

Here’s the most important thing to understand: PARP inhibitors are approved as maintenance therapy, not as a standalone treatment. Maintenance therapy is what comes after your chemotherapy for ovarian cancer has worked. The goal is to hold that response in place for as long as possible and delay ovarian cancer recurrence.

Approval also depends on your tumor’s biology. Two terms will come up in that conversation:

• BRCA-mutated (BRCAm). Your tumor carries a harmful mutation in BRCA1 or BRCA2. This can be inherited (germline) or acquired by the tumor itself (somatic).
• HRD-positive. HRD stands for homologous recombination deficiency. A tumor is HRD-positive if it carries a BRCA mutation or shows genomic instability on an FDA-approved companion diagnostic test. In other words, every BRCA-mutated tumor is HRD-positive, but not every HRD-positive tumor has a BRCA mutation.

That distinction now decides who is eligible. Which is exactly why genetic testing and tumor profiling aren’t optional extras; they’re the gatekeeper to this entire class of drugs.

The approved settings

First-line maintenance after platinum-based chemotherapy. For patients with newly diagnosed advanced ovarian cancer who responded to their first round of platinum-based chemotherapy, a PARP inhibitor may be used to delay recurrence. Eligibility depends on the specific drug and on whether your tumor is BRCA-mutated or HRD-positive.

Maintenance in recurrent disease. For patients whose cancer has come back and who responded to platinum-based chemotherapy again, maintenance with a PARP inhibitor is an option — now restricted to patients with a BRCA mutation.

What changed, and why it matters

The rules here have tightened considerably since PARP inhibitors first arrived, and older articles on the internet still describe approvals that no longer exist.

Beginning in 2022, the FDA reviewed mature overall survival data from several pivotal trials and narrowed these indications. Manufacturers issued “Dear Healthcare Provider” letters for rucaparib, olaparib, and niraparib, and the single-agent treatment approvals for recurrent ovarian cancer were withdrawn. Later-line and non-BRCA maintenance uses were restricted as well.

More recently, niraparib’s first-line maintenance indication — once approved regardless of biomarker status — was restricted at the FDA’s request to patients with HRD-positive disease, following the final analysis of the PRIMA trial.

The pattern is consistent: these drugs deliver real benefit for the right patients, and the FDA has steadily sharpened the definition of “right.” That’s not a step backward. It’s precision medicine doing its job. But it does mean you should be talking with a gynecologic oncologist about your biomarker results.

Types of PARP Inhibitors for Ovarian Cancer

Three PARP inhibitors are FDA-approved for ovarian cancer in the United States. All three are taken orally. Their approved uses are no longer interchangeable.

Olaparib (Lynparza)

Olaparib was the first PARP inhibitor approved for ovarian cancer, and it currently carries the broadest set of ovarian indications. It is approved as:

• First-line maintenance for adults with BRCA-mutated (germline or somatic) advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy
• First-line maintenance in combination with bevacizumab for advanced ovarian cancer that is HRD-positive and responded to first-line platinum-based chemotherapy
• Maintenance for adults with BRCA-mutated (germline or somatic) recurrent ovarian cancer who are in complete or partial response to platinum-based chemotherapy

That second bullet is the one most often missing from older patient-facing articles. If your oncologist has mentioned pairing olaparib with bevacizumab (Avastin), this is the indication they’re working from.

Niraparib (Zejula)

Niraparib is approved as first-line maintenance for adults with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy and whose cancer is HRD-positive: defined by a deleterious or suspected deleterious BRCA mutation and/or genomic instability. Patients are selected using an FDA-authorized companion diagnostic.

This is a meaningful change from niraparib’s original 2020 approval, which did not require biomarker testing.

Rucaparib (Rubraca)

Rucaparib’s ovarian cancer indication is now limited to maintenance treatment for adults with a deleterious BRCA mutation (germline or somatic) associated with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, who are in complete or partial response to platinum-based chemotherapy. It is not approved for first-line maintenance in ovarian cancer.

Are they all the same drug?

Not quite. Olaparib, rucaparib, and niraparib all block the PARP enzyme, but each has its own chemical structure. That means the body may absorb, distribute, and clear each one differently. Side effect profiles and dosing schedules differ, too.

Your gynecologic oncologist will weigh your cancer type, BRCA and HRD status, treatment history, overall health, other medications, and how you’re likely to tolerate each option. If the recommendation isn’t clear to you, ask why this drug and not another. It’s a fair question, and a good oncologist will welcome it.

Are PARP Inhibitors Used for Low-Grade Serous Ovarian Cancer or Borderline Tumors?

This is the question we hear most often from our community, and the honest answer is: usually not.

Nearly all the research behind PARP inhibitors was conducted in high-grade serous ovarian cancer, a disease defined by genomic instability, near-universal TP53 mutation, and frequent defects in homologous recombination repair. Roughly half of high-grade serous tumors are HRD-positive. That’s the vulnerability PARP inhibitors were designed to exploit.

Low-grade serous ovarian cancer (LGSOC) and borderline ovarian tumors (BOTs) are biologically different diseases. LGSOC has a stable genome and a low mutational burden. Its pathogenesis is strongly associated with activation of the MAPK pathway, with mutually exclusive mutations in KRAS, BRAF, or NRAS detected in roughly half to 60% of cases: mutations that often arise early, in serous borderline tumors. Germline BRCA1/2 mutations are rare in LGSOC.

No BRCA mutation, no HRD, no synthetic lethality. The mechanism that makes PARP inhibitors so powerful in high-grade disease simply doesn’t have much to grab onto in low-grade serous or borderline tumors.

So where does that leave patients with these subtypes? Not without options, but with far fewer of them, and with treatments that target a completely different pathway:

• MEK and BRAF inhibitors, which act on the MAPK pathway. Learn more about BRAF and MEK inhibitors and about trametinib specifically.
• The avutometinib and defactinib combination, the first FDA-approved treatment for a specific subset of LGSOC. Read our full guide to avutometinib and defactinib.
• Hormonal therapies, since LGSOC is frequently estrogen-receptor positive.
• Surgery, which remains central to borderline ovarian tumor treatment.

If you have LGSOC or a borderline tumor, ask your gynecologic oncologist about molecular tumor profiling. Knowing whether your tumor carries a KRAS, BRAF, or NRAS mutation opens doors that BRCA testing alone will not.

How to Prepare for Treatment with PARP Inhibitors

Before starting treatment with a PARP inhibitor, your doctor will recommend genetic and tumor testing to determine your BRCA and HRD status. This information doesn’t just guide the decision; under the current approvals, it is the decision. Companion diagnostic testing is required for several of these indications.

Your gynecologic oncologist and healthcare team will also discuss the potential ovarian cancer treatment side effects of PARP inhibitors and how to manage them. You must report any side effects you experience during treatment to your doctor so they can help you manage them effectively.

PARP inhibitors are administered orally in pill form, meaning you can take them at home. Your doctor will provide specific instructions on taking the medication, such as the dosage, frequency, and any special considerations (e.g., taking with or without food). Some PARP inhibitors also interact with other medications, so give your care team a complete list of everything you take, including supplements.

How Long Will You Take a PARP Inhibitor?

Maintenance therapy isn’t forever, and knowing the finish line helps.

First-line maintenance is generally given for a defined period rather than indefinitely. For olaparib, that period is commonly around two years, with the option to continue longer if imaging shows evidence of disease and your doctor believes you’re still benefiting. In the PRIMA trial, niraparib maintenance was studied over a longer window — up to three years — making it the longest maintenance duration evaluated in the pivotal first-line trials.

Your actual duration depends on the drug, your response, and how well you tolerate treatment. Dose reductions and treatment breaks are common and are not a sign of failure. Many patients stay on therapy successfully after an adjustment.

Ask your oncologist directly: How long do you expect me to be on this? What would make you stop it early? What happens to my monitoring when I finish? Write the answers down.

What Monitoring Will You Need During Treatment?

PARP inhibitors affect the bone marrow, so blood work becomes a routine part of your life on treatment.

Expect a complete blood count before you start and monthly thereafter, watching for anemia, low platelets, and low white blood cell counts. If your counts drop, your team may pause treatment, reduce your dose, or hold the drug until you recover. Prolonged low counts get investigated further, sometimes with a referral to a hematologist.

You’ll also continue the follow-up care that comes with any ovarian cancer treatment plan: scheduled visits, CA-125 monitoring, and periodic imaging. Between appointments, call your team about unusual bruising, bleeding, shortness of breath, or fatigue that suddenly worsens. Don’t wait for the next scheduled visit to mention it.

What Does a PARP Inhibitor Cost?

Oral cancer drugs are often billed through pharmacy benefits rather than medical benefits, which can mean significant out-of-pocket costs even with good insurance. It’s a genuine barrier, and it’s one you should raise early rather than after the first bill arrives.

A few things to know:

• Each manufacturer runs a patient support program offering financial assistance, copay help, and reimbursement navigation. Ask your oncology team or pharmacist to connect you.
• Prior authorization is common. Your biomarker test results are frequently what unlocks coverage, which is another reason to make sure testing is complete and documented.
• Oncology social workers and financial navigators exist for exactly this. Most cancer centers have them, and most patients never ask.

For a broader look at managing expenses across your whole treatment journey, see our guide to ovarian cancer treatment cost.

Potential Side Effects of PARP Inhibitors

Like all cancer treatments, PARP inhibitors can cause side effects. Some of the most common side effects include:

• Fatigue
• Nausea and vomiting
• Anemia (low red blood cell count)
• Thrombocytopenia (low platelet count)
• Neutropenia (low white blood cell count)
• Decreased appetite
• Diarrhea or constipation
• Headache
• Dizziness
• Insomnia

Most side effects are manageable with supportive care or by adjusting the dose of the PARP inhibitor. However, in rare cases, PARP inhibitors can cause more serious side effects, such as myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). These conditions affect the blood and bone marrow and can be life-threatening. It’s crucial to report any unusual symptoms to your healthcare team promptly.

Why Do PARP Inhibitors Stop Working Sometimes?

While PARP inhibitors have shown remarkable success in treating ovarian cancer, they don’t work for everyone. Some patients never respond to these drugs at all, which is known as primary resistance. Others respond well at first, then find the treatment gradually loses effectiveness over time (acquired resistance).

Understanding why these treatments stop working involves several complex mechanisms. One of the main reasons PARP inhibitors lose their effectiveness is the development of secondary mutations in the BRCA genes or other genes involved in DNA repair. These mutations can restore the cancer cell’s ability to repair DNA damage, essentially undermining the primary mechanism by which PARP inhibitors work.

Cancer cells can also develop other sophisticated ways to resist treatment. Some cells learn to pump the drug out more efficiently, while others alter how they metabolize the medication or change how the drug is transported within the cell.

The environment around the tumor itself can also play a crucial role in resistance, with changes in blood vessel formation, immune cell activity, and oxygen levels all potentially affecting how well PARP inhibitors work.

Additionally, cancer cells may activate alternative survival pathways or develop protective mechanisms that allow them to survive despite DNA damage.

Researchers are actively working to overcome these resistance challenges through various approaches. This includes exploring combinations of PARP inhibitors with other targeted therapies or chemotherapy agents, developing new generations of PARP inhibitors that can bypass resistance mechanisms, and identifying ovarian cancer biomarkers that might predict which patients are more likely to develop resistance.

Scientists are also testing drug combinations that target multiple resistance mechanisms simultaneously, aiming to improve the long-term effectiveness of PARP inhibitor therapy and help more patients benefit from these treatments.

Much of that work happens inside clinical trials. If you’re wondering whether one might be right for you, start with the benefits of ovarian cancer clinical trials.

PARP Inhibitors and the Path to Better Outcomes for Ovarian Cancer Patients

PARP inhibitors have revolutionized the treatment landscape for ovarian cancer, offering a targeted approach that exploits the unique vulnerabilities of cancer cells with DNA repair defects.

By blocking the PARP enzyme’s ability to repair DNA damage, these drugs cause an accumulation of DNA damage that ultimately leads to cancer cell death. PARP inhibitors have shown particularly promising results in treating ovarian cancers with BRCA mutations, improving progression-free survival and quality of life for many patients.

As research continues to unravel the complexities of PARP inhibitor resistance and explore new strategies to enhance their effectiveness, the future of ovarian cancer treatment looks increasingly hopeful. Combining PARP inhibitors with other targeted therapies, immunotherapies, or chemotherapy agents may help overcome resistance and improve outcomes for more patients.

Ovarian cancer patients must work closely with their healthcare team to determine if PARP inhibitors are a suitable treatment option. Genetic testing for BRCA mutations, discussing potential side effects, and understanding the treatment process are all crucial steps in making informed decisions about their care.

At Not These Ovaries, we understand the importance of advancing ovarian cancer research and bringing new, effective treatments to patients as quickly as possible. Our non-profit organization is dedicated to growing our ovarian cancer research fund and funding clinical trials to improve outcomes and quality of life for those affected by this disease. 

If you or a loved one has been diagnosed with ovarian cancer, know that you are not alone. With the rapid advancements in targeted therapies like PARP inhibitors, there is reason to be optimistic about the future of ovarian cancer treatment. Don’t hesitate to contact your healthcare team, support organizations, or our team at Not These Ovaries for information, support, and guidance on your journey.