What are PARP Inhibitors
Precision medicine has transformed cancer care. Targeted therapies that inhibit specific molecular pathways driving cancer growth have improved survival and quality of life for many patients. Poly (ADP-ribose) polymerase or PARP inhibitors are an important class of targeted agents showing promise in battling various cancers.PARP enzymes are involved in DNA damage repair. Poly (ADP-ribose) polymerase (PARP) is a family of proteins involved in DNA repair. When DNA is damaged by environmental factors, radiation, chemicals or during DNA replication, PARP enzymes help detect the damaged DNA and recruit repair proteins to the site of damage. PARP inhibitors are a class of targeted anti-cancer drugs that work by blocking the actions of PARP enzymes. This prevents cancer cells from effectively repairing damage to their DNA and can ultimately lead to cancer cell death.
Mechanism of Action
PARP inhibitors work by trapping PARP enzymes onto DNA strands at sites of single-strand DNA breaks. This blocks access for other repair proteins and prevents DNA repair from occurring normally. In cancer cells already harboring defects in homologous recombination repair (HRR) pathway genes such as BRCA1 and BRCA2, this leads to accumulation of irreparable DNA damage and cell death by synthetic lethality. By depriving cancer cells of a critical DNA repair pathway, PARP inhibitors can selectively kill tumor cells while sparing normal cells. This dual targeting approach confers potent anticancer activity with a good safety profile.
Coherent Market Insights takes a deeper look at PARP inhibitors – what they are, how they work, current applications and future potential PARP Inhibitor Market.
Current Applications
- Ovarian Cancer: The first FDA-approved use of PARP inhibitors is for treating recurrent ovarian cancer. BRCA mutations are found in about 20% of ovarian cancers and PARP inhibitors show significant clinical benefit for these patients. Lynparza (olaparib) and Rubraca (rucaparib) are approved as maintenance treatment for recurrent platinum-sensitive ovarian cancer patients with a BRCA mutation.
- Breast Cancer: PARP inhibitors have utility in advanced BRCA-mutated breast cancer as well. Talzenna (talazoparib) is FDA-approved for germline BRCA-mutated, HER2-negative locally advanced or metastatic breast cancer previously treated with chemotherapy. OlympiAD trial data recently led to accelerated approval of Lynparza for this indication.
- Prostate Cancer: Emerging data show PARP inhibitors may benefit prostate cancer patients too. Clinical trials are exploring their role in metastatic castration-resistant prostate cancer either as monotherapy or in combination with androgen deprivation/targeted therapies.
- Other Cancers: Preclinical evidence suggests PARP inhibitors may help fight certain lung, pancreatic and other cancers driven by defective HRR genes. Ongoing research aims to expand their reach to more cancer types.
Combination Strategies
Studies increasingly evaluate PARP inhibitors combined with chemotherapy, immunotherapy, radiation therapy and other targeted drugs. Synergistic effects are observed when combining with DNA damaging agents like platinum drugs or radiation. Combining with immune checkpoint inhibitors also generates interest due to interplay between DNA damage response and immune signaling pathways. Such rational combinations hold promise to maximize clinical benefit from PARP inhibitors across a wider span of cancer patients.
Market Outlook
For more details on the market potential and factors influencing growth, refer to the market research report published on Coherent Market Insights. Major revenue contributors were the U.S., Japan, France, Germany and Italy. Increasing FDA approvals for new indications, growing clinical evidence, emerging combination strategies and rising healthcare expenditures are projected to sustain double-digit market expansion during the forecast period. However, patent expiry of first-generation drugs and entry of biosimilars may provide some restraint. Nonetheless, continued R&D into better understanding molecular determinants of response and resistance will further broaden the eligible patient population and market prospects for PARP inhibitors.
