How does Lynparza (olaparib) work?
Lynparza is a PARP inhibitor. It blocks PARP enzymes—especially PARP1 and PARP2—which normally help repair single-strand DNA breaks. When PARP is inhibited, damaged DNA is more likely to convert into double-strand breaks during cell division. Cancer cells that already have defective DNA repair (commonly due to BRCA1/BRCA2 mutations) rely more heavily on PARP-mediated repair, so they accumulate DNA damage and die. [1]
Why does Lynparza work better in BRCA-mutated cancers?
BRCA1 and BRCA2 are involved in homologous recombination, a major pathway for repairing double-strand DNA breaks. If BRCA function is lost, the cell’s ability to fix double-strand breaks drops. With PARP blocked, the resulting DNA damage becomes lethal for these tumor cells because they cannot switch to efficient double-strand break repair. [1]
What does “PARP inhibition” mean at the DNA-repair level?
PARP proteins help detect DNA damage and facilitate repair processes for single-strand breaks. Inhibiting PARP both reduces repair of those breaks and can increase “PARP trapping,” where PARP stays bound to damaged DNA and interferes with replication. Together, this pushes cells toward lethal genomic instability, particularly in tumors already deficient in homologous recombination. [1]
What happens in cells after Lynparza treatment?
The main downstream effect is increased accumulation of DNA damage. As replication proceeds, unresolved lesions lead to DNA replication stress, double-strand breaks, and failure to maintain genomic integrity, which triggers cell death. [1]
Is Lynparza only for BRCA mutations?
PARP inhibition is most effective when tumors depend on PARP-mediated repair, such as in homologous recombination deficiency (HRD). BRCA mutations are a common example, but other HRD contexts can also be relevant because the underlying vulnerability is the reduced ability to repair double-strand breaks. [1]
Sources
[1] https://www.drugs.com/mechanism-of-action/lynparza-olaparib.html