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 (such as the proteins BRCA1 and BRCA2) is compromised, as in many 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 can cause DNA damage to accumulate to the point where the cancer cell can no longer survive, making them a potential treatment option for some patients.

Who can benefit from PARP inhibitors?

PARP inhibitors have been approved by the U.S. Food and Drug Administration for the treatment of some forms of breast, fallopian tube, ovarian, pancreatic, primary peritoneal, and prostate cancer.

The PARP inhibitors that have been approved by the U.S. Food and Drug Administration include olaparib, rucaparib, niraparib, and talazoparib.

What are the side effects of PARP inhibitors?

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 targeted therapies, not 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.

An example is a recent study led by Panagiotis Konstantinopoulos, MD, PhD, and Ursula Matulonis, MD, that found that many patients with endometrial cancer marked by mutations in an array of genes involved in double-stranded DNA repair responded well to a combination of talazoparib and the immunotherapy drug avelumab. Patients who responded to prior treatment with platinum-based chemotherapy for at least six months also responded well to the combination.

What is the current state of research into PARP inhibitors?

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: