{"entity":{"id":"paper-lord-science","kind":"paper","name":"PARP inhibitors: Synthetic lethality in the clinic","aka":[],"tldr":"Paper cited by three pathway pages, indexed on Europe PMC as PubMed record 28302823 and published in Science; the citing pages link this DOI, which is how the record was matched.","summary":"PARP inhibitors (PARPi), a cancer therapy targeting poly(ADP-ribose) polymerase, are the first clinically approved drugs designed to exploit synthetic lethality, a genetic concept proposed nearly a century ago. Tumors arising in patients who carry germline mutations in either BRCA1 or BRCA2 are sensitive to PARPi because they have a specific type of DNA repair defect. PARPi also show promising activity in more common cancers that share this repair defect. However, as with other targeted therapies, resistance to PARPi arises in advanced disease. In addition, determining the optimal use of PARPi within drug combination approaches has been challenging. Nevertheless, the preclinical discovery of PARPi synthetic lethality and the route to clinical approval provide interesting lessons for the development of other therapies. Here, we discuss current knowledge of PARP inhibitors and potential ways to maximize their clinical effectiveness.\n\nIndexed on Europe PMC as PubMed record 28302823 (DOI 10.1126/science.aam7344). Matched by DOI alone: three pathway pages cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Science 2017","url":"https://doi.org/10.1126/science.aam7344"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28302823/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/28302823"}],"tags":["europepmc-ingest"],"related":["base-excision-repair-parp","homologous-recombination-repair","synthetic-lethality-map"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["science"],"dependsOn":[],"notes":[],"journal":"Science","year":2017,"doi":"10.1126/science.aam7344","pmid":"28302823","authors":"Lord CJ, Ashworth A","paperType":"review","findings":[],"whatItMeans":"Three pathway pages on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},"route":"/key-papers/paper-lord-science/","neighbours":{"pathway":[{"id":"base-excision-repair-parp","kind":"pathway","name":"Base excision repair, PARP & alkylation damage","route":"/pathways/base-excision-repair-parp/"},{"id":"homologous-recombination-repair","kind":"pathway","name":"Double-strand break repair: HR versus end joining","route":"/pathways/homologous-recombination-repair/"},{"id":"synthetic-lethality-map","kind":"pathway","name":"Synthetic lethality: paired dependencies","route":"/pathways/synthetic-lethality-map/"}],"journal":[{"id":"science","kind":"journal","name":"Science","route":"/journals/science/"}]}}