Liquid biopsy based HER2 amplification status in gastric cancer patients indicates clinical response

  • \(\underline {Gastric}\) \(\underline {carcinomas}\) are among the most common cancers in Germany, with approximately 18,000 new cases per year. About 10 years ago, based on results of the \(\underline {Trastuzumab}\) for gastric cancer (ToGA) trial, the addition of the \(\underline {monoclonal}\) \(\underline {antibody}\) trastuzumab to a platinum-fluoropyrimidine chemotherapy \(\underline {backbone}\) became the standard-of-care 1st-line \(\underline {therapy}\) for human \(\underline {epidermal}\) \(\underline {growth}\) \(\underline {factor}\) \(\underline {receptor}\) 2 (\(\it HER2\))-positive gastric cancers. Only patients with primary \(\it HER2\) \(\underline {gene}\) \(\underline {amplification}\) benefit from this therapy. Thus, accurate \(\it HER2\) gene amplification detection is predictive and critical for therapy selection. As a gold standard the \(\it HER2\) status is currently determined in tumor tissue specimens using immune \(\underline {histochemistry}\) and \(\underline {fluorescent}\) \(\underline {in}\) \(\underline {situ}\) \(\underline {hybridisation}\). However, \(\it HER2\) amplification is detectable in only about 20 % of gastric carcinomas. The recent approval of an antibody-drug conjugate \(\underline {Trastuzumab}\) \(\underline {deruxtecan}\) (T-DXd) and the establishment of a new subgroup of \(\it HER2\)-low tumors due to the \(\underline {bystander}\) \(\underline {effect}\) associated with T-DXd increases the relevance of precise \(\it HER2\) diagnostics. Aim of this analysis was to determine the \(\it HER2\) amplification status from circulating DNA fragments in blood using a \(\it HER2\) \(\underline {Copy}\) \(\underline {Number}\) \(\underline {Variation}\) assay to establish a minimal invasive approach. For the present study, a digital droplet PCR-based method was validated relative to established tissue-based methods. Furthermore and most importantly, the changes of \(\it HER2\) status during therapy were investigated in seven patients indicating that the changes of \(\it HER2\) status and number of \(\it HER2\) copies detected in blood can reflect on therapy efficiency and uncover treatment resistance.

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Author:Susanne Klein-ScoryORCiDGND, Swetlana Ladigan-BaduraORCiDGND, Thomas MikaORCiDGND, Berlinda VerdoodtGND, Andrea TannapfelORCiDGND, Michael PohlORCiDGND, Roland SchroersORCiDGND, Alexander BaraniskinGND
Parent Title (English):Heliyon
Publisher:Elsevier B.V.
Place of publication:Amsterdam
Document Type:Article
Date of Publication (online):2024/03/21
Date of first Publication:2023/11/02
Publishing Institution:Ruhr-Universität Bochum, Universitätsbibliothek
Tag:Open Access Fonds
Issue:11, Artikel e21339
First Page:e21339-1
Last Page:e21339-9
Article Processing Charge funded by the Deutsche Forschungsgemeinschaft (DFG) and the Open Access Publication Fund of Ruhr-Universität Bochum.
Institutes/Facilities:Knappschaftskrankenhaus Bochum
Dewey Decimal Classification:Technik, Medizin, angewandte Wissenschaften / Medizin, Gesundheit
open_access (DINI-Set):open_access
faculties:Medizinische Fakultät
Licence (English):License LogoCreative Commons - CC BY 4.0 - Attribution 4.0 International