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

Autor: Susanne Klein-Scory, Swetlana Ladigan-Badura, Thomas Mika, Berlinda Verdoodt, Andrea Tannapfel, Michael Pohl, Roland Schroers, Alexander Baraniskin
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Heliyon, Vol 9, Iss 11, Pp e21339- (2023)
Druh dokumentu: article
ISSN: 2405-8440
DOI: 10.1016/j.heliyon.2023.e21339
Popis: Gastric 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 Trastuzumab for gastric cancer (ToGA) trial, the addition of the monoclonal antibody trastuzumab to a platinum-fluoropyrimidine chemotherapy backbone became the standard-of-care 1st-line therapy for human epidermal growth factor receptor 2 (HER2)-positive gastric cancers. Only patients with primary HER2 gene amplification benefit from this therapy. Thus, accurate HER2 gene amplification detection is predictive and critical for therapy selection. As a gold standard the HER2 status is currently determined in tumor tissue specimens using immune histochemistry and fluorescent in situ hybridisation. However, HER2 amplification is detectable in only about 20 % of gastric carcinomas. The recent approval of an antibody-drug conjugate Trastuzumab deruxtecan (T-DXd) and the establishment of a new subgroup of HER2-low tumors due to the bystander effect associated with T-DXd increases the relevance of precise HER2 diagnostics.Aim of this analysis was to determine the HER2 amplification status from circulating DNA fragments in blood using a HER2 Copy Number 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 HER2 status during therapy were investigated in seven patients indicating that the changes of HER2 status and number of HER2 copies detected in blood can reflect on therapy efficiency and uncover treatment resistance.
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