A PARP inhibitor is a type of cancer drug that works by blocking a protein your cells use to repair damaged DNA. When this repair system is shut down, cancer cells with existing DNA repair defects accumulate so much genetic damage that they die. These drugs are primarily used to treat ovarian, breast, prostate, and pancreatic cancers, especially in people whose tumors carry specific genetic mutations like BRCA1 or BRCA2.
How PARP Inhibitors Kill Cancer Cells
Your cells constantly sustain minor DNA damage, and a protein called PARP1 is one of the first responders. It detects small breaks in a single strand of DNA and helps patch them up. This is routine maintenance that happens in every cell, every day.
A PARP inhibitor blocks that repair process. In healthy cells, this isn’t a major problem because they have backup repair systems, including one called homologous recombination, that can fix the damage through a different route. But cancer cells with BRCA1 or BRCA2 mutations have a broken backup system. When PARP is also blocked, unrepaired single-strand breaks pile up. As cells divide and copy their DNA, those small breaks become catastrophic double-strand breaks. With no reliable way to fix them, the cancer cell dies.
This concept is called synthetic lethality: losing either PARP function or BRCA function alone is survivable, but losing both at the same time is fatal to the cell. It’s what makes PARP inhibitors a targeted therapy. They exploit a weakness that exists in the cancer but not in normal tissue, which is why side effects, while real, tend to be more manageable than traditional chemotherapy.
PARP inhibitors also work through a second mechanism called PARP trapping. Rather than simply blocking PARP from working, the drug physically locks the PARP protein onto the DNA strand. This trapped complex becomes a roadblock that stalls the machinery cells use to copy DNA, creating even more damage during cell division.
Who Is Eligible for Treatment
Not every cancer patient is a candidate for a PARP inhibitor. These drugs work best in tumors that already have a defect in DNA repair, so testing for specific genetic markers is a critical step before treatment.
The most established biomarker is a mutation in the BRCA1 or BRCA2 genes. In high-grade ovarian cancer, for instance, BRCA1 mutations are found in 12% to 15% of cases, and BRCA2 mutations in 5% to 7%. These mutations can be inherited (germline) or arise only in the tumor itself (somatic), and both types can make a patient eligible.
Beyond BRCA, doctors may test for a broader condition called homologous recombination deficiency, or HRD. This means the tumor’s DNA repair pathway is impaired for any number of reasons: mutations in related genes like RAD51C, RAD51D, or PALB2, or chemical modifications that silence the BRCA1 gene. HRD testing typically uses one of two approaches. The first looks for mutations in specific repair genes. The second scans the tumor’s genome for patterns of accumulated damage, sometimes called “genomic scars,” that indicate repair has been defective over time. Two commercially available tests combine both approaches and are widely used to guide treatment decisions.
Your oncologist will generally order this testing at diagnosis or when considering maintenance therapy after chemotherapy. The results determine not just whether a PARP inhibitor is appropriate, but how much benefit you’re likely to see from it.
Cancers Treated With PARP Inhibitors
Three PARP inhibitors have received broad approval for cancer treatment: olaparib, niraparib, and rucaparib. All three are oral medications taken as pills or capsules, typically once or twice daily.
Ovarian cancer is the most established use. PARP inhibitors are approved both as maintenance therapy after a patient responds to platinum-based chemotherapy and as treatment for recurrent disease. In the SOLO1 trial, which studied olaparib as maintenance therapy in newly diagnosed ovarian cancer with BRCA mutations, the risk of disease progression or death dropped by 70% compared to placebo over a median follow-up of 41 months. The PAOLA-1 trial, which combined olaparib with another targeted therapy, showed a 41% reduction in the risk of progression.
These drugs are also approved for certain breast cancers, pancreatic cancers, and prostate cancers that carry BRCA mutations. The most recent approval, in December 2025, was a combination of niraparib with a hormone therapy for metastatic prostate cancer with BRCA2 mutations. The range of eligible cancers continues to expand as clinical trials identify new populations that benefit.
Common Side Effects
Because PARP inhibitors interfere with DNA repair across the body, they affect rapidly dividing healthy cells too, particularly blood cells and the cells lining the digestive tract.
Gastrointestinal symptoms like nausea, vomiting, and loss of appetite are among the most frequent side effects, often appearing within the first few weeks. About 70% of patients experience these as mild, and only 3% to 4% develop severe gastrointestinal problems. Nausea tends to improve over time and can usually be managed with anti-nausea medication.
Blood-related side effects are the more serious concern. Anemia (low red blood cells), low platelet counts, and low white blood cell counts are all common. In one major trial of niraparib, 25% of patients developed severe anemia after five to six cycles of treatment. These effects require regular blood monitoring, and your oncologist may adjust the dose or pause treatment temporarily if your counts drop too low. Fatigue is also very common and may be partly related to anemia, partly an independent effect of the drug.
How Resistance Develops
PARP inhibitors can be highly effective, but many cancers eventually find ways to survive despite the drug. Understanding how this happens is one of the most active areas of cancer research.
The most common route is straightforward: the cancer cell repairs its original BRCA mutation. Called reversion mutations, these genetic changes restore the cell’s ability to fix double-strand DNA breaks, eliminating the very vulnerability the drug was designed to exploit. Reversion mutations are detected in roughly 50% to 80% of patients with BRCA-mutant tumors who initially respond but later relapse.
Cancer cells can also develop resistance without restoring BRCA function. Some protect their DNA replication machinery from collapsing under stress. Others pump the drug out of the cell before it can work. Recent research has identified yet another mechanism: mutations in the machinery cells use to prepare for DNA copying (called the prereplication complex) can allow cancer cells to quickly resolve drug-induced DNA damage, even without functional BRCA. In prostate cancer, about 50% of advanced tumors show reduced activity of these prereplication genes, which may partially explain why some patients don’t respond as expected.
When resistance develops, oncologists may switch to a different class of therapy, combine the PARP inhibitor with other drugs, or consider newer, more selective PARP inhibitors currently in clinical trials that may overcome some resistance mechanisms.