PARP inhibitors
PARP inhibitors are small-molecule drugs that block PARP enzymes, which cancer cells use to repair damaged DNA. They are particularly active against tumors that already have a faulty DNA-repair pathway — most often due to BRCA1 or BRCA2 mutations — because such cells lose their last reliable repair route and die. Olaparib, for example, is approved in defined settings for ovarian, breast, pancreatic, and prostate cancers, usually after testing confirms the relevant mutation.
How it works
Every cell constantly repairs small breaks in its DNA, and enzymes called PARP handle one of the main repair routes. A second, more thorough route — homologous recombination — depends on working BRCA1 and BRCA2 genes. In many ovarian, breast, pancreatic, and prostate cancers a BRCA mutation has already disabled that second route, so the cancer cell relies entirely on PARP.
A PARP inhibitor blocks that remaining route: unrepaired single-strand breaks turn into double-strand breaks when the cell divides, and a cell that cannot fix them dies. Healthy cells with intact BRCA genes still have their backup route, which is why the drug hits the tumor harder than normal tissue — a principle researchers call synthetic lethality. NCI materials also note that some inhibitors additionally "trap" PARP on the DNA, deepening the damage. These drugs are typically offered after biomarker testing confirms a BRCA or related repair-pathway mutation.
Used in
Ovary & Fallopian Tube
C56-C57
established maintenance treatment, particularly with a BRCA mutation
Pancreas
C25
olaparib maintenance is an option in metastatic disease with a germline BRCA mutation