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Exploring PARP Inhibitors: Insights into Their Role

NextEdge Admin

25 Dec 2023

3 min 30 sec

Poly(ADP-ribose) polymerase (PARP) inhibitors are a class of drugs used in the treatment of certain cancers, particularly those associated with BRCA gene mutations. PARP is an enzyme involved in DNA repair, and when PARP is inhibited, it prevents cancer cells from repairing their damaged DNA. This is particularly significant in cancer cells that already have a compromised ability to repair DNA due to mutations, such as those with BRCA1 or BRCA2 gene mutations.

Here’s how PARP inhibitors work:

1. Normal DNA Repair Process: In normal cells, the DNA repair process involves various mechanisms, including the activity of PARP enzymes.

2. DNA Damage in Cancer Cells: Cancer cells, especially those with BRCA mutations, have a defective DNA repair mechanism. They heavily rely on alternative repair pathways, such as the PARP-dependent pathway.

3. PARP Inhibition: PARP inhibitors block the activity of the PARP enzyme, preventing cancer cells from using this alternative repair pathway.

4. Synthetic Lethality: In cells with BRCA mutations, inhibiting PARP becomes particularly lethal. These cells are already deficient in one DNA repair pathway (due to BRCA mutation), and blocking another (PARP-dependent) leads to the accumulation of unrepaired DNA damage, ultimately causing cell death.

Examples of PARP inhibitors include:

1. Olaparib (Lynparza)

2. Rucaparib (Rubraca)

3. Niraparib (Zejula)

4. Talazoparib (Talzenna)

Indications for PARP Inhibitors:

1. BRCA-Mutated Ovarian Cancer: PARP inhibitors are used as a treatment for advanced ovarian cancer in individuals with BRCA1 or BRCA2 gene mutations.

2. Breast Cancer with BRCA Mutations: In certain cases of breast cancer with BRCA1 or BRCA2 mutations, PARP inhibitors may be prescribed.

3. Prostate Cancer: PARP inhibitors like olaparib are indicated for the treatment of metastatic castration-resistant prostate cancer in individuals with specific genetic alterations.

4. Pancreatic Cancer: Some PARP inhibitors have shown efficacy in the treatment of metastatic pancreatic cancer with certain genetic mutations.

5. Maintenance Therapy: PARP inhibitors, such as niraparib, may be used as maintenance therapy in recurrent ovarian, fallopian tube, or primary peritoneal cancer.

6. Advanced Solid Tumors: Research is ongoing to explore the potential use of PARP inhibitors in various advanced solid tumors with specific genetic markers.