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Combined targeting of HER-2 and HER-3 represents a promising therapeutic strategy in colorectal cancer

dc.contributor.authorConradi, Lena-Christin
dc.contributor.authorSpitzner, Melanie
dc.contributor.authorMetzger, Anna-Lena
dc.contributor.authorKisly, Merle
dc.contributor.authorMiddel, Peter
dc.contributor.authorBohnenberger, Hanibal
dc.contributor.authorGaedcke, Jochen
dc.contributor.authorGhadimi, Michael B
dc.contributor.authorLiersch, Torsten
dc.contributor.authorRüschoff, Joseph
dc.contributor.authorBeißbarth, Tim
dc.contributor.authorKönig, Alexander
dc.contributor.authorGrade, Marian
dc.description.abstractAbstract Background 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) receptors HER-2 and HER-3 in the three cell lines LS513, LS1034 and SW837. Methods 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. Results 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 5-fluorouracil and oxaliplatin. Finally, high expression of HER-3 was detected in 121 of 172 locally advanced rectal cancers (70.3%). 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. Conclusion Since HER-2 and HER-3 are expressed in a relevant number of patients, targeting both receptors may represent a promising therapeutic strategy for CRC.
dc.description.sponsorshipOpen-Access-Publikationsfonds 2019
dc.publisherBioMed Central
dc.identifier.bibliographicCitationBMC Cancer. 2019 Sep 05;19(1):880
dc.titleCombined targeting of HER-2 and HER-3 represents a promising therapeutic strategy in colorectal cancer
dc.rights.holderThe Author(s).
dc.bibliographicCitation.journalBMC Cancer

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