What Does PARP Inhibitor Mean?

PARP stands for poly (ADP-ribose) polymerase. It is an enzyme in cells that helps repair damaged DNA.

A PARP inhibitor is a drug that blocks that enzyme. NCI explains that blocking PARP may keep cancer cells from repairing their damaged DNA, so they die. PARP inhibitors are a type of targeted therapy.

Cancer cells with harmful changes in the BRCA1 or BRCA2 genes already have trouble repairing DNA. Scientists call the effect of adding a PARP inhibitor synthetic lethality. A cell can survive either problem alone, but not both together. That is why the phrase "PARP inhibitor" almost never appears in a report by itself. It appears next to a gene result.

NCI lists four PARP inhibitors approved by the FDA to treat certain cancers with harmful BRCA1 or BRCA2 changes. Each is approved only for specific situations.

• Olaparib (Lynparza). Approved uses include certain HER2-negative breast cancers with an inherited BRCA change, maintenance for ovarian, fallopian tube and primary peritoneal cancers, some metastatic pancreatic cancers with an inherited BRCA change, and some prostate cancers that have spread.
• Rucaparib (Rubraca). Approved as maintenance for some ovarian, fallopian tube and primary peritoneal cancers with a BRCA change, and for some prostate cancers with a BRCA change that have spread.
• Niraparib (Zejula). Approved as maintenance for some ovarian, fallopian tube and primary peritoneal cancers that responded to platinum chemotherapy.
• Talazoparib (Talzenna). Approved for some HER2-negative breast cancers with an inherited BRCA change, and, with enzalutamide, for some prostate cancers that have spread.

Read this as background. Approved uses change over time. Your oncologist decides which drug and what dose fit you. Never change your tablets based on this page.

The term usually enters a chart in one of three ways.

A genomic test result. A pathology report or tumor sequencing report notes a BRCA1 or BRCA2 alteration, and the report's interpretation section flags PARP inhibitors as a class with matching evidence. That is a laboratory comment, not a prescription.

A germline genetics result. An inherited BRCA finding from a blood or saliva test carries the same flag, and it also has implications for relatives.

A treatment plan or tumor board note. Here the term does mean a decision is being made, usually about maintenance treatment after platinum chemotherapy.

If you cannot tell which of the three you are reading, look at who signed the document. A laboratory director signs a report. An oncologist signs a plan.

Seeing "PARP inhibitor" in a report does not mean you qualify for one, and it does not tell you which one. The choice depends on your cancer type, whether the BRCA change is inherited or only in the tumor, what chemotherapy you already had, how you responded to it, your blood counts, and your kidney function.

It also does not mean the drug is being started now. Many uses are maintenance, meaning the drug begins after another treatment has already shrunk the cancer.

The FDA labels list side effects for each drug. Common ones across the group include nausea, tiredness, anemia (low red cells), vomiting, diarrhea, loss of appetite, headache, shortness of breath, and low white cells or platelets.

Some serious effects deserve names of their own.

Bone marrow effects. All four labels warn about myelodysplastic syndrome and acute myeloid leukemia (MDS/AML), disorders of blood-forming cells. Some cases were fatal. This is why blood counts are checked on a schedule, not only when you feel unwell.

Other label warnings. The olaparib label warns about pneumonitis (lung inflammation), blood clots including clots in the lung, and liver injury. The niraparib label warns about high blood pressure and heart effects. All four can harm an unborn baby, so the labels advise effective birth control.

A temperature of 100.4 degrees F (38 degrees C) or higher needs a call right away. CDC says a fever during chemotherapy is a medical emergency and to call your doctor immediately. These drugs can lower the white cells that fight infection. If you go to the emergency room, tell staff you are getting cancer treatment. NCI says to talk with your doctor or nurse before taking medicine to lower a fever, because it can hide signs of a more serious problem.

Go to an emergency department, or call 911, for these:

• Sudden chest pain, or breathlessness that comes on quickly. A clot in the lung behaves like this, and so can severe pneumonitis.
• Bleeding you cannot stop, or black or tarry stools. Low platelets can turn ordinary bleeding into a serious one.

Call your care team right away for these:

• A dry cough that keeps getting worse, or breathlessness building over days. These can signal pneumonitis.
• Swelling, warmth, or pain in one calf. That pattern suggests a clot in the leg.
• Bruising without injury, nosebleeds, or gums that bleed when brushing. These point to low platelets.
• Yellowing of the eyes or skin, or dark urine. These point to the liver.

• Which gene change was found, and was it inherited or only in the tumor?
• Which PARP inhibitor is being considered, and at what dose?
• Is this maintenance after chemotherapy, or treatment on its own?
• How often will my blood counts and liver tests be checked?
• What dose reduction happens if my counts drop, rather than stopping outright?
• Does my result mean my siblings or children should be tested?

For related reading, see BRCA Gene Mutations Explained, Biomarker Testing and Precision Medicine, and Living With a PARP Inhibitor Day to Day.

• National Cancer Institute — BRCA Gene Changes: Cancer Risk and Genetic Testing
• NCI Dictionary of Cancer Terms — PARP inhibitor
• NCI — Olaparib
• NCI — Rucaparib Camsylate
• NCI — Niraparib Tosylate Monohydrate
• NCI — Talazoparib Tosylate
• DailyMed — FDA drug labels
• National Cancer Institute — Infection and Neutropenia during Cancer Treatment
• CDC — Fever and Cancer Treatment