How Do PARP Inhibitors Work In Cancer?

PARPs (or Poly (ADP-ribose) polymerases) are proteins that play an important role in the life of a cell. When a strand of the DNA double helix is broken or damaged, PARPs act as a repair crew to help fix the damaged site, allowing the cell to live.

PARPs are particularly important when another repair crew (which includes the BRCA1 and BRCA2 proteins) is compromised, which happens frequently in cancer cells. When BRCA1 or BRCA2 is not functioning well, cancer cells depend on PARPs to remain alive, grow, and divide.

Drugs that inhibit or stop PARPs from doing their job cause the breakdown of a second repair crew (besides that of BRCA1/BRCA2), which cannot be tolerated by cancer cells, thereby creating a potential treatment option for some patients.

What cancers can PARP inhibitors work for?

As of early 2020, four PARP inhibitors have received Food and Drug Administration approval as standard treatment for some cancers: olaparib, rucaparib, and niraparib for ovarian cancer, and olaparib and talazoparib for breast cancer.

What are the side effects of PARP inhibitors?

PARP can play an important role in DNA repair.

The most common adverse side effect of PARP inhibitor treatment is anemia. Other side effects vary from one drug to another, but can include:

  • Fatigue
  • Nausea
  • Diarrhea
  • Headache
  • Decreased appetite
  • Dizziness
  • Insomnia
  • Rash

Your care team can work with you to help minimize these effects.

Do PARP inhibitors cause hair loss?

PARP inhibitors are classified as a form of targeted therapy and, unlike some types of chemotherapy, generally do not cause hair loss. 

Are PARP inhibitors considered immunotherapy?

Because PARP inhibitors strike at cancer cells’ DNA-repair machinery and do not directly target the immune system, they are not considered immunotherapies.

However, recent research at Dana-Farber indicates that PARP inhibitors may also stimulate the immune system to attack some ovarian cancers. The findings suggest that combining PARP inhibitors with certain immunotherapy agents may extend remissions beyond what PARP inhibitors can achieve alone.

What is the current state of research?

Clinical trials are currently testing PARP inhibitors in combination with other treatments including radiation therapy, chemotherapy, and angiogenesis inhibitors (which reduce tumors’ ability to grow new blood vessels).

Currently, there are also clinical trials exploring the use of PARP inhibitors in patients with prostate cancer, pancreatic cancer, triple-negative breast cancer, and other cancer types.

Watch this short illustrated video to see how PARP inhibitors work: