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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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.
KeywordsGastric cancer HER2 Immunohistochemistry Liver metastasis Lymph node metastasis Resistance
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).
Conflicts of interests
- 8.Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010;376(9742):687–97.CrossRefPubMedGoogle Scholar
- 22.Thomadsen B, Erwin W, Mourtada F. The physics and radiobiology of targeted radionuclide therapy. In: Speer TW, editor. Targeted radionuclide therapy. Lippincott Williams & Wilkins, Philadelphia; 2011, Chapter 6, pp. 71–87Google Scholar
- 30.Sobin LH, Wittekind C, editors. TNM classification of malignant tumours. 6th ed. New York: Wiley-Liss; 2002. p. 239.Google Scholar
- 32.Hamilton SR, Aaltonen LA. World Health Organization and International Agency for Research on Cancer. Pathology and genetics of tumours of the digestive system. Lyon: IARC; 2000. p. 313.Google Scholar
- 35.Sörensen J, Sandberg D, Sandström M, Wennborg A, Feldwisch J, Tolmachev V, et al. First in human whole body HER2-receptor mapping using Affibody 111In-ABY-025 molecular imaging. J Nucl Med. (In press), 2014.Google Scholar
- 36.Altai M, Orlova A, Tolmachev V. Radiolabeled Probes Targeting Tyrosine-Kinase Receptors For Personalized Medicine. Curr Pharm Des. 2013 (In press).Google Scholar
- 58.Ståhl S, Friedman M, Carlsson J, Tolmachev V, Frejd F. Affibody molecules for targeted radionuclide therapy. In: Speer TW, editor. Targeted radionuclide therapy. Lippincott Williams & Wilkins; 2011. Chapter 4, pp. 49-58.Google Scholar