Universität zu Köln

Schmitt, Anna, Feldmann, Georg, Zander, Thomas and Reinhardt, H. Christian (2018). Targeting Defects in the Cellular DNA Damage Response for the Treatment of Pancreatic Ductal Adenocarcinoma. Oncol. Res. Treat., 41 (10). S. 619 - 626. BASEL: KARGER. ISSN 2296-5262

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Abstract

Pancreatic cancer is one of the most common causes of cancer-related mortality in the Western world and pancreatic ductal adenocarcinoma (PDAC) is by far the most common pancreatic cancer entity. Locally advanced or metastatic PDAC remains a major clinical challenge, and the prognosis of affected patients is dismal despite substantial research efforts in this area. Recent large-scale genomic analyses of PDAC revealed that KRAS is the most frequently mutated driver gene in this entity. In addition, a relatively large proportion of PDAC patients displays germline variants in genes involved in DNA repair, particularly DNA double-strand repair. Similarly, a sizable fraction of sporadic PDAC cases harbor mutations in genome maintenance genes, such as BRCA1, BRCA2, and ATM. While direct targeting of oncogenic KRAS is currently not possible in the clinical setting, these defects in DNA repair may open new therapeutic avenues. Here, we discuss the potential use of compounds that interfere with DNA repair and genome maintenance mechanisms for the treatment of PDAC. We particularly focus on the genotype-tailored use of compounds, such as PARP inhibitors, as well as ATR- and DNA-protein kinase catalytic subunit (PKcs) inhibitors. (C) 2018 S. Karger GmbH, Freiburg.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Schmitt, Anna UNSPECIFIED UNSPECIFIED UNSPECIFIED Feldmann, Georg UNSPECIFIED UNSPECIFIED UNSPECIFIED Zander, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Reinhardt, H. Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-201892
DOI:	10.1159/000493401
Journal or Publication Title:	Oncol. Res. Treat.
Volume:	41
Number:	10
Page Range:	S. 619 - 626
Date:	2018
Publisher:	KARGER
Place of Publication:	BASEL
ISSN:	2296-5262
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SYNTHETIC LETHAL INTERACTION; STRAND BREAK REPAIR; HOMOLOGOUS RECOMBINATION; STK33 KINASE; GERMLINE MUTATIONS; CANCER STATISTICS; GENOMIC ANALYSES; ATM DEFICIENCY; MEK INHIBITION; PATHWAYS Multiple languages Oncology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/20189