Cancer hijacks the body’s natural processes of cell growth, division, and death, turning healthy cells into rogue ones that grow uncontrollably, evade death, and eventually invade nearby tissues or spread to distant parts of the body (metastasis). Chemotherapy and radiation therapy are two of the most widely used—and most aggressive—tools in cancer treatment. Unfortunately, these two treatments kill healthy cells in the process of killing the cancer cells. Researchers are always searching for treatments that kill cancer but spare healthy cells; one of these modalities is PARP inhibitors (Poly ADP-Ribose Polymerase inhibitors). These are a class of drugs used primarily to treat certain cancers by targeting the way cancer cells repair their DNA. These drugs are revolutionary because they can kill cancer cells while leaving healthy cells unharmed. The downside of PARP inhibitors is that they aren’t effective for all cancers.
What is PARP?
PARP is a family of enzymes—with PARP-1 being the most well-known—that play a critical role in repairing single-strand breaks in DNA. When DNA is damaged (which happens naturally or from cancer treatments), PARP enzymes help fix it.
How PARP Inhibitors Work
PARP inhibitors block these enzymes, preventing cancer cells from repairing their damaged DNA. If a cancer cell can’t fix its DNA, it accumulates damage and eventually dies. This is especially effective in cancer cells that already have deficiencies in other DNA repair pathways, like those with BRCA1 or BRCA2 mutations.
This mechanism is a strategy called synthetic lethality:
- Normal cells can survive because they have backup DNA repair systems.
- Cancer cells with faulty BRCA genes can’t repair DNA effectively, and when PARP is also blocked, they die.
Types of PARP Inhibitors
Approved drugs include:
- Olaparib (Lynparza)
- Rucaparib (Rubraca)
- Niraparib (Zejula)
- Talazoparib (Talzenna)
Each has slightly different characteristics, but they all inhibit PARP enzymes.
What Cancers Are They Used For?
- Ovarian cancer
- Breast cancer (especially with BRCA mutations)
- Prostate cancer
- Pancreatic cancer
They’re often used in:
- Patients with BRCA1 or BRCA2 mutations
- As maintenance therapy after chemotherapy
- Sometimes in combination with other drugs or immunotherapies
Benefits and Limitations
Benefits:
- Targets cancer cells specifically, sparing many healthy cells
- Often used orally (pill form)
- Extends progression-free survival in several cancers
Side Effects:
- Nausea, fatigue, anemia, decreased appetite
- Risk of blood disorders like myelodysplastic syndrome (MDS) in rare cases
- GI symptoms (constipation, diarrhea)
PARP inhibitors are a powerful, targeted cancer therapy that work by disabling cancer cells’ DNA repair mechanisms, especially in tumors already weakened by genetic mutations like BRCA. They’re revolutionizing treatment in cancers where traditional chemo once dominated. Hopefully, in the future, more treatments will arise that have the same ability as PARP inhibitors do of sparing healthy cells, but will be able to kill any cancer cell, not just those with gene mutations. While PARP inhibitors are a significant part of the future of cancer treatment, they are not the whole story. They’re one of several key pillars in a shift toward precision oncology, where therapies are chosen based on the genetic makeup of the cancer, not just its location.
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