When you’re diagnosed with ovarian cancer, you may hear about targeted treatments called PARP inhibitors. We asked UCLA Health’s Dr. Beth Karlan to explain how they work, who they are most helpful for, and whether they might be part of your treatment plan.
What are PARP inhibitors?
Dr. Karlan explains, “PARP stands for polyadenosine ribose polymerase.” PARP proteins are enzymes that help fix damage to DNA. Small breaks in DNA happen all the time as we go about our daily lives.
“Whether it’s sunlight, whether it’s diet, we get DNA breaks as part of living our lives,” she continues. Normally, enzymes like PARP help repair that damage so cells can continue functioning normally.
Ovarian cancer cells can also use PARP to grow and spread. PARP inhibitors block this repair system and can be very effective.
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Why PARP inhibitors work for some patients
Some patients with ovarian cancer have trouble repairing DNA. Dr. Karlan shares that this is often due to inherited or acquired genetic changes, such as mutations in the BRCA1 or BRCA2 genes, or a condition called homologous recombination deficiency (HRD). Importantly, healthy cells usually don’t have the same repair defects.
This is why PARP inhibitors are considered targeted therapies—they’re designed to affect cancer cells more than healthy ones.
Why PARP inhibitors aren’t for everyone
When PARP inhibitors were first studied, researchers explored whether they might benefit all ovarian cancer patients.
However, clinical trials showed that the greatest benefit was in patients whose tumors had BRCA mutations or HRD. In people without those genetic features, the risks sometimes outweighed the benefits.
Dr. Karlan explains that studies found patients without HRD experienced more side effects and didn’t see the same survival benefits. As a result, treatment guidelines and regulatory approvals were updated.
How PARP inhibitors are used in ovarian cancer treatment
Most commonly, PARP inhibitors are used as maintenance therapy. This means they’re given after chemotherapy once the cancer is in remission, to help delay the cancer from coming back.
Dr. Karlan notes that current recommendations often involve taking a PARP inhibitor for about two years during this maintenance phase.
Researchers are continuing to study whether shorter treatment durations could still be effective. Dr. Karlan adds that some clinical trials are exploring whether one year of therapy might be enough, which could reduce side effects for some patients.
Possible side effects to know about
Although PARP inhibitors are taken as pills, they are still powerful cancer treatments and can cause side effects.
Some of the more common ones include:
- Fatigue
- Nausea
- Anemia (low red blood cells), which may sometimes require transfusions
- Changes in taste
Dr. Karlan explains that dysgeusia, or a persistent bad taste in the mouth, can affect many patients.
She often sees patients notice a difference once they stop treatment: “They come back that next visit… and they say, ‘Wow. I didn’t realize how much more energy I have, how much better food tastes, and how I’m getting back to myself again.’”
A rare but serious risk is the development of certain blood cancers, such as leukemia. While this is uncommon, doctors carefully monitor blood counts during treatment.
As Dr. Karlan emphasizes, “Just because it’s an oral medication, there are lots of side effects.” Your care team will weigh these risks against the potential benefits when recommending treatment.
The importance of personalized treatment
PARP inhibitors can be an important tool for many patients, but they are most effective when used in the right situation. Talking with your care team about your tumor’s genetics, treatment goals, and potential side effects can help you decide whether this therapy fits into your care plan.
See the full discussion with Dr. Karlan here.
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