Over the past decade, a new class of drugs called PARP inhibitors have been approved by the Food and Drug Administration (FDA) for use in ovarian cancer. Three FDA-approved PARP inhibitors — as well as others that are still under investigation — have offered hope for patients and clinicians in their quest to cure ovarian cancer. Understanding what these drugs are, how they work and who benefits most from taking them can help ovarian cancer patients navigate their treatment options.
What is a PARP Inhibitor?
PARP inhibitors block a protein called poly adenosine diphosphate-ribose polymerase, or PARP. In some cancer cells, blocking PARP can keep the cells from dividing and replicating.
To function and reproduce correctly, the cells in your body are constantly copying and proofreading their DNA. When cells detect errors or breaks in the DNA, they activate repair machinery to fix these errors before copying again. There are a few different types of DNA repair machinery. In around half of all ovarian cancers — including those with mutations in the BRCA genes — cancer cells are defective in one type of repair mechanism. But PARP fixes damaged DNA using a different mechanism.
This means that PARP inhibitors, by blocking PARP, can keep cancer cells from having any kind of DNA repair mechanism and thus from copying and multiplying. Healthy cells, however, are largely unaffected by the drugs since they have a backup repair mechanism that works.
History of PARP Inhibitors
In 2005, two basic research studies published in the journal Nature concluded that cancers with BRCA mutations, including ovarian and breast cancer, could be treated by blocking PARP. Clinical trials testing this idea were carried out and, in 2014, the first PARP inhibitor — Olaparib (Lynparza) — was approved by the FDA for use in patients with BRCA-mutated metastatic ovarian cancer following three or more rounds of chemotherapy. By 2018, two more PARP inhibitors — rucaparib (Rubraca) and niraparib (Zejula) — had been approved for ovarian cancer.
PARP Inhibitors for Ovarian Cancer
PARP inhibitors are currently approved to treat ovarian cancer patients with and without BRCA mutations and other related genetic defects, called homologous recombination deficient (HRD) ovarian cancer.
In some cases, PARP inhibitors are given to patients with advanced, recurrent or metastatic disease that is not responding to other therapies. However, the drugs are also now prescribed as a maintenance treatment — this means they are given to patients with advanced epithelial cancers and high-grade serous ovarian cancer after chemotherapy has already decreased the size of their tumor. Studies have shown that this can delay or prevent recurrence of ovarian cancer.
Taking PARP Inhibitors
PARP inhibitors are generally prescribed as tablets or capsules, taken twice a day. How long a patient takes them for depends on their exact type of ovarian cancer.
Studies have established that PARP inhibitors are safe but, like all drugs, they can lead to side effects. The most common side effects of PARP inhibitors include:
- An increased risk of infection and bleeding problems
- Diarrhea or indigestion
- Taste changes
- Headaches and dizziness
- Liver and kidney problems
PARP Inhibitor Research
Research is ongoing into how else PARP inhibitors can help treat ovarian cancer. OCRA-funded research on PARP inhibitors is examining — among many other things — how some ovarian cancers become resistant to PARP inhibitors, what other drugs might work best in combination with PARP inhibitors, and how PARP inhibitors could be used even in ovarian cancer patients without BRCA mutations or homologous recombination deficiencies. Researchers also want to develop better tests to determine who will most benefit from taking PARP inhibitors.