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Titel:

Synergistic targeting and resistance to PARP inhibition in DNA damage repair-deficient pancreatic cancer.

Dokumenttyp:
Article; Journal Article; Research Support, Non-U.S. Gov't
Autor(en):
Gout, Johann; Perkhofer, Lukas; Morawe, Mareen; Arnold, Frank; Ihle, Michaela; Biber, Stephanie; Lange, Sebastian; Roger, Elodie; Kraus, Johann M; Stifter, Katja; Hahn, Stephan A; Zamperone, Andrea; Engleitner, Thomas; Müller, Martin; Walter, Karolin; Rodriguez-Aznar, Eva; Sainz, Bruno; Hermann, Patrick C; Hessmann, Elisabeth; Müller, Sebastian; Azoitei, Ninel; Lechel, André; Liebau, Stefan; Wagner, Martin; Simeone, Diane M; Kestler, Hans A; Seufferlein, Thomas; Wiesmüller, Lisa; Rad, Roland; Fr...     »
Abstract:
OBJECTIVE: ATM serine/threonine kinase (ATM) is the most frequently mutated DNA damage response gene, involved in homologous recombination (HR), in pancreatic ductal adenocarcinoma (PDAC). DESIGN: Combinational synergy screening was performed to endeavour a genotype-tailored targeted therapy. RESULTS: Synergy was found on inhibition of PARP, ATR and DNA-PKcs (PAD) leading to synthetic lethality in ATM-deficient murine and human PDAC. Mechanistically, PAD-induced PARP trapping, replication fork s...     »
Zeitschriftentitel:
Gut
Jahr:
2021
Band / Volume:
70
Heft / Issue:
4
Seitenangaben Beitrag:
743-760
Volltext / DOI:
doi:10.1136/gutjnl-2019-319970
PubMed:
http://view.ncbi.nlm.nih.gov/pubmed/32873698
Print-ISSN:
0017-5749
TUM Einrichtung:
Klinik und Poliklinik für Innere Medizin II, Gastroenterologie (Prof. Schmid); Professur für Molekulare Onkologie und Funktionelle Genomik (Prof. Rad)
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