Evaluation von Anti-HER-2-Substanzen für die Therapie des kolorektalen Karzinoms

Metzger, Anna-Lena Clara

dc.contributor.advisor	Grade, Marian PD Dr.
dc.contributor.author	Metzger, Anna-Lena Clara
dc.date.accessioned	2020-09-29T12:09:38Z
dc.date.available	2020-11-10T23:50:02Z
dc.date.issued	2020-09-29
dc.identifier.uri	http://hdl.handle.net/21.11130/00-1735-0000-0005-1498-9
dc.identifier.uri	http://dx.doi.org/10.53846/goediss-8226
dc.identifier.uri	http://dx.doi.org/10.53846/goediss-8226
dc.language.iso	deu	de
dc.rights.uri	http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.ddc	610	de
dc.title	Evaluation von Anti-HER-2-Substanzen für die Therapie des kolorektalen Karzinoms	de
dc.type	doctoralThesis	de
dc.title.translated	Evaluation of targeting HER-2 as a therapeutic strategy in colorectal cancer	de
dc.contributor.referee	Kube, Dieter Prof. Dr.
dc.date.examination	2020-11-03
dc.description.abstracteng	Abrogation of growth factor-dependent signaling represents an effective therapeutic strategy for patients with colorectal cancer (CRC). Here we evaluated the effectiveness of targeting the epidermal growth factor (EGF) receptor HER-2 in the three cell lines LS513, LS1034 and SW837. Treatment with HER-2-specific antibodies trastuzumab and pertuzumab resulted in a mild reduction of cellular viability. In contrast, the antibody-drug conjugate T-DM1 mediated a strong and dose-dependent decrease of viability and Akt phosphorylation. The most striking effects were observed with the dual tyrosine kinase inhibitor lapatinib, and the Pan-ErbB inhibitor afatinib. Selectively, the effect of EGF receptor inhibition was augmented by a combination with 5fluorouracil and oxaliplatin. In conclusion, inhibition of EGF receptors effectively blocks downstream signaling and significantly impairs viability of CRC cells. However, the effectiveness of receptor inhibition highly depends on the inhibitors’ mode of action, as targeting HER-2 alone is not sufficient. Since HER-2 is expressed in a relevant number of patients, targeting this receptors may represent a promising therapeutic strategy for CRC.	de
dc.contributor.coReferee	Oppermann, Martin Prof. Dr.
dc.subject.ger	Kolorektales Karzinom	de
dc.subject.ger	zielgerichtete Therapie	de
dc.subject.ger	HER-2	de
dc.subject.eng	Colorectal cancer	de
dc.subject.eng	HER-2	de
dc.subject.eng	Targeted therapy	de
dc.subject.eng	Inhibitors	de
dc.identifier.urn	urn:nbn:de:gbv:7-21.11130/00-1735-0000-0005-1498-9-5
dc.affiliation.institute	Medizinische Fakultät	de
dc.subject.gokfull	Abdominalchirurgie (PPN619875976)	de
dc.subject.gokfull	GOK-MEDIZIN	de
dc.description.embargoed	2020-11-10
dc.identifier.ppn	1733968601

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