PARP
PARP is a DNA repair enzyme. Cancers that have already lost one repair system (BRCA) die when this second one is blocked; healthy cells survive.
Overview
PARP inhibitors (olaparib, niraparib, rucaparib, talazoparib) exploit synthetic lethality with BRCA1/2 mutations and homologous recombination deficiency in ovarian, breast, prostate, and pancreatic cancer. Olaparib is approved in adjuvant germline-BRCA breast cancer (OlympiA). PARP1-selective inhibitors (saruparib) and PARP PET tracers are the next step.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · PARP is a DNA repair enzyme. Cancers that have already lost one repair system (BRCA) die when this second one is blocked; healthy cells survive.
- 1 · What it is
PARP is a DNA repair enzyme. Cancers that have already lost one repair system (BRCA) die when this second one is blocked; healthy cells survive.
- 2 · What goes wrong in cancer
Poly(ADP-ribose) polymerase 1 senses single-strand breaks; trapping on DNA is the key cytotoxic mechanism.
- 3 · How drugs use it
1 product aims at PARP: small molecules. Inhibitors are shaped to fit the enzyme's active site so the reaction the cancer relies on stops.
External identifiers
Companion diagnostics
- FoundationOne CDx · Per companion claim: EGFR, ALK, BRAF V600, ERBB2 amplification, KRAS wild-type, BRCA1/2 and HRR genes, PIK3CA, MET exon 14, RET, FGFR2 fusions, IDH1, NTRK fusions; MSI-high; TMB at least 10 mutations per megabase
- BRACAnalysis CDx · Deleterious or suspected deleterious germline variant
- myChoice CDx · Genomic instability score at least 42, or BRCA1/2 mutation, defines HRD-positive (olaparib plus bevacizumab, PAOLA-1; niraparib)
- FoundationFocus CDxBRCA · Deleterious BRCA1/2 alteration (rucaparib, ovarian cancer)
Biology
Poly(ADP-ribose) polymerase 1 senses single-strand breaks; trapping on DNA is the key cytotoxic mechanism.
- BRCA/HRD ovarian, breast, prostate, pancreatic cancers
How often this target appears
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Prostate cancer | 20-25% | HRR gene alteration (mCRPC) | BRCA2 ~8-10% | cBioPortal (TCGA) |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
Olaparib was the first PARP inhibitor, and turned an inherited BRCA mutation from a risk factor into a drug target, including after surgery in breast cancer.
Latest papers
topQuery for this target: (TITLE:"PARP" OR ABSTRACT:"PARP" OR TITLE:"PARP1" OR ABSTRACT:"PARP1" OR TITLE:"PARP1/2" OR ABSTRACT:"PARP1/2" OR TITLE:"Poly [ADP-ribose] polymerase 2" OR ABSTRACT:"Poly [ADP-ribose] polymerase 2") AND (radiopharmaceutical OR radioligand OR radionuclide OR theranostic OR "nuclear medicine" OR "molecular imaging" OR radiotracer OR scintigraphy OR cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about PARP, not a curated reading list.
Similar pages
not linked directly; found by shared links- IdeaAdding a PARP inhibitor to PSMA radioligand therapy
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- TrialFPI-2265 (225Ac-PSMA-I&T) and Olaparib for Patients With Metastatic Castration-Resistant Prostate Cancer (mCRPC)
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- InstitutionThe Royal Marsden
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- CompanyMerck & Co. (MSD)
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- PersonLouise Emmett
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- PersonShahneen Sandhu
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- CompanyAstraZeneca
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