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HER2 expression in primary gastric cancers and paired synchronous lymph node and liver metastases. A possible road to target HER2 with radionuclides

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Tumor Biology

Abstract

Resistance has been reported to human epidermal growth factor receptor 2 (HER2)-targeted therapy with the tyrosine kinase inhibitor lapatinib and the antibody trastuzumab in metastatic gastric cancer. An alternative or complement might be to target the extracellular domain of HER2 with therapy-effective radionuclides. The fraction of patients with HER2 expression in primary tumors and major metastatic sites, e.g., lymph nodes and liver, was analyzed to evaluate the potential for such therapy. Samples from primary tumors and lymph node and liver metastases were taken from each patient within a few hours, and to our knowledge, such sampling is unique. The number of analyzed cases was therefore limited, since patients that had received preoperative radiotherapy, chemotherapy, or HER2-targeted therapy were excluded. From a large number of considered patients, only 29 could be included for HER2 analysis. Intracellular mutations were not analyzed since they are assumed to have no or minor effect on the extracellular binding of molecules that deliver radionuclides. HER2 was positive in nearly 52 % of the primary tumors, and these expressed HER2 in corresponding lymph node and liver metastases in 93 and 100 % of the cases, respectively. Similar values for primary tumors and also good concordance with metastases have been indicated in the literature. Thus, relevant radionuclides and targeting molecules for nuclear medicine-based noninvasive, whole-body receptor analysis, dose planning, and therapy can be applied for many patients; see “Discussion” Hopefully, more patients can then be treated with curative instead of palliative intention.

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Acknowledgments

Financial support was given from the National Natural Science Foundation of China (contracts 81071823 and 81201811), Zhejiang University Research foundation, China (contract 11-491020-110), and the Swedish Cancer Society, Sweden (contracts 11-0565 and 12-0415).

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Authors and Affiliations

  1. Department of Radiation Oncology, The Second Affiliated Hospital and Cancer Institute (National Ministry of Education Key Laboratory of Cancer Prevention and Intervention), Zhejiang University School of Medicine, 310009, Hangzhou, People’s Republic of China

    Qichun Wei, Jing Xu, Li Shen, Xianhua Fu, Bicheng Zhang & Xiaofeng Zhou

  2. Department of Radiology Oncology and Radiation Science, Rudbeck Laboratory, Unit of Biomedical Radiation Sciences, Uppsala University, 751 85, Uppsala, Sweden

    Jorgen Carlsson

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  1. Qichun Wei
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Correspondence to Jorgen Carlsson.

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Wei, Q., Xu, J., Shen, L. et al. HER2 expression in primary gastric cancers and paired synchronous lymph node and liver metastases. A possible road to target HER2 with radionuclides. Tumor Biol. 35, 6319–6326 (2014). https://doi.org/10.1007/s13277-014-1830-3

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