Parp Inhibitor AZD2281

• AZD2281 (olaparib) is a PARP inhibitor, a type of targeted cancer therapy.
• Its primary mechanism involves blocking DNA repair pathways, specifically in cancer cells with existing DNA repair deficiencies.
• It is predominantly used in the treatment of various cancers, including ovarian, breast, pancreatic, and prostate cancers, particularly those with BRCA mutations or other homologous recombination repair (HRR) gene alterations.
• AZD2281 leverages the concept of synthetic lethality to selectively kill cancer cells while sparing healthy ones.

What is Parp Inhibitor AZD2281?

Parp Inhibitor AZD2281 is an oral medication classified as a poly (ADP-ribose) polymerase (PARP) inhibitor. PARP enzymes play a crucial role in DNA repair, specifically in the base excision repair pathway, which is vital for fixing single-strand DNA breaks. By inhibiting these enzymes, AZD2281 prevents cancer cells from effectively repairing their DNA, leading to an accumulation of DNA damage.

This drug is particularly effective in cancers that already have defects in other major DNA repair pathways, such as homologous recombination repair (HRR), often due to mutations in genes like BRCA1 or BRCA2. This phenomenon is known as synthetic lethality, where the inhibition of PARP becomes lethal to cells that cannot rely on alternative repair mechanisms, while healthy cells with intact HRR pathways can still repair DNA damage. According to the National Cancer Institute, approximately 10-15% of ovarian cancers and 5-10% of breast cancers are associated with inherited BRCA mutations, making PARP inhibitors a critical treatment strategy for these patient populations.

AZD2281: Mechanism of Action and Uses

The AZD2281 mechanism of action involves binding to and inhibiting PARP-1 and PARP-2 enzymes. This inhibition prevents PARP from repairing single-strand DNA breaks. When these unrepaired single-strand breaks are encountered during DNA replication, they are converted into more severe double-strand breaks. In cancer cells with a compromised homologous recombination repair pathway (e.g., due to BRCA mutations), these double-strand breaks cannot be effectively repaired, leading to genomic instability and ultimately, programmed cell death (apoptosis). Furthermore, AZD2281 also causes PARP trapping, where the drug binds to PARP and traps it on the DNA, further impeding DNA replication and repair.

The primary Parp Inhibitor AZD2281 uses span several types of cancer, often as a maintenance therapy or for recurrent disease in patients with specific genetic mutations. Its approved indications include:

• Ovarian Cancer: For maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to first-line platinum-based chemotherapy and have a deleterious or suspected deleterious germline or somatic BRCA mutation. It is also used for recurrent, platinum-sensitive ovarian cancer.
• Breast Cancer: For the treatment of adult patients with germline BRCA-mutated, HER2-negative metastatic breast cancer who have been previously treated with chemotherapy.
• Pancreatic Cancer: For the maintenance treatment of adult patients with germline BRCA-mutated metastatic pancreatic adenocarcinoma whose disease has not progressed on at least 16 weeks of a first-line platinum-based chemotherapy regimen.
• Prostate Cancer: For the treatment of adult patients with deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC) who have progressed following prior treatment with enzalutamide or abiraterone.

As for AZD2281 drug information, it is administered orally, typically as tablets, and the dosage is determined by a healthcare professional based on the patient’s specific condition and tolerance. Common side effects can include fatigue, nausea, vomiting, anemia, and abdominal pain. Regular monitoring of blood counts and liver function is necessary during treatment. Patients should always consult their oncologist for comprehensive information regarding treatment protocols and potential side effects.