Universität zu Köln

Hescheler, Daniel A., Plum, Patrick S. ORCID: 0000-0002-8165-4553, Zander, Thomas, Quaas, Alexander, Korenkov, Michael, Gassa, Asmae, Michel, Maximilian ORCID: 0000-0002-5910-5363, Bruns, Christiane J. and Alakus, Hakan (2020). Identification of targeted therapy options for gastric adenocarcinoma by comprehensive analysis of genomic data. Gastric Cancer, 23 (4). S. 627 - 639. NEW YORK: SPRINGER. ISSN 1436-3305

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Abstract

Background So far only trastuzumab, pembrolizumab and ramucirumab have been approved by the FDA for targeted therapy in gastric cancer (GC). Here we report on potential targeted therapy options for gastric adenocarcinoma based on a novel analysis of The Cancer Genome Atlas (TCGA) database. Methods One hundred two FDA-approved targeted cancer drugs were compiled and molecular targets defined. Drugs were considered as potentially effective if targeted genes showed (1) an increase in copy number, (2) gain of function with oncogene activation, (3) specific alterations responsive to approved drugs. Additionally, genetic changes that confer drug resistance and/or sensitivity were evaluated. Results Fifty percentage of patients with GC may be treatable with non-GC but FDA-approved targeted cancer therapies. The major drug identified in our in silico study for GC is copanlisib, a PI3K inhibitor. In the TCGA patient database, our genetically based drug response prediction identified more patients with alterations sensitive to copanlisib compared to the already-GC-approved drug trastuzumab (20%, 78 out of 393 patients, vs. trastuzumab: 13%, 52 of 393 patients), which is mainly due to the high incidence of PIK3CA gain of function mutations within mutation hot spots. Conclusion Our results demonstrate that various currently FDA-approved drugs might be candidates for targeted therapy of GC. For clinical trials, cancer patients should be selected based on the genomic profile of their tumor.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Hescheler, Daniel A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Plum, Patrick S. UNSPECIFIED orcid.org/0000-0002-8165-4553 UNSPECIFIED Zander, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Quaas, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Korenkov, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Gassa, Asmae UNSPECIFIED UNSPECIFIED UNSPECIFIED Michel, Maximilian UNSPECIFIED orcid.org/0000-0002-5910-5363 UNSPECIFIED Bruns, Christiane J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Alakus, Hakan UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-343895
DOI:	10.1007/s10120-020-01045-9
Journal or Publication Title:	Gastric Cancer
Volume:	23
Number:	4
Page Range:	S. 627 - 639
Date:	2020
Publisher:	SPRINGER
Place of Publication:	NEW YORK
ISSN:	1436-3305
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PHASE-II; PLUS PACLITAXEL; CANCER; HETEROGENEITY; MULTICENTER; REGORAFENIB; MONOTHERAPY; MUTATIONS; MEDICINE; IMATINIB Multiple languages Oncology; Gastroenterology & Hepatology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/34389