Detection of HER2 Amplification in Circulating Tumor Cells of HER2-Negative Gastric Cancer Patients
| Autor: | Tomoko Takayama, Yasuhito Terui, Keisho Chin, Mariko Mikuniya, Nobuyuki Mizunuma, Satoshi Matsusaka, Sayuri Minowa, Kiyohiko Hatake, Yuji Mishima, Mariko Ogura, Harumi Shibata, Ryoko Kuniyoshi |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Oncology Adult Cancer Research medicine.medical_specialty Pathology Carcinogenesis Receptor ErbB-2 Somatic evolution in cancer Biomarkers Pharmacological 03 medical and health sciences 0302 clinical medicine Circulating tumor cell Antineoplastic Agents Immunological Trastuzumab Stomach Neoplasms Internal medicine Biopsy medicine Humans Pharmacology (medical) Prospective Studies Stage (cooking) skin and connective tissue diseases Prospective cohort study neoplasms Aged Neoplasm Staging Aged 80 and over medicine.diagnostic_test business.industry Patient Selection Gene Amplification Cancer Middle Aged medicine.disease Prognosis Primary tumor 030104 developmental biology 030220 oncology & carcinogenesis Blood Circulation Immunotherapy business medicine.drug |
| Zdroj: | Targeted oncology. 12(3) |
| ISSN: | 1776-260X |
| Popis: | A key to the successful use of targeted cancer therapy is the ability to preselect patients who are likely to benefit from the treatment according to molecular markers. Assessment for predicting therapy response is mostly done using tumor biopsies. However, these might not truly represent all of the patient’s malignant cells because of tumor heterogeneity and/or clonal evolution during disease progression. One potential strategy that can complement primary tumor biopsy is the analysis of circulating tumor cells (CTCs). In this study, we analyzed CTCs of patients with gastric cancer (GC) to find those who were likely to benefit from trastuzumab therapies. We developed an imaging-based method that enabled CTC identification simultaneously with evaluation of HER2 gene amplification (the 3D–IF-FISH method). Then we performed a study enrolling 101 GC patients in whom we analyzed CTCs by both 3D–IF-FISH and an FDA-approved CellSearch system. As compared with the CellSearch system, 3D–IF-FISH methods identified a higher number of patients whose primary tumors were HER2- but who had HER2+ CTCs, suggesting that the 3D–IF-FISH method is effective in preselecting patients for trastuzumab therapies. To demonstrate this, we performed an exploratory clinical study to evaluate the clinical benefits of trastuzumab treatment for advanced GC patients (n = 15) whose primary tumors were HER2-, but whose CTCs showed HER2 amplification. An interim evaluation after the first stage showed that these preselected patients had response rates comparable to those reported in the trastuzumab-plus-chemotherapy arm of the ToGA study. The present study offers a new, non-invasive strategy to select patients who are likely to benefit from trastuzumab-based therapies, despite their primary biopsy being HER2-negative. (UMIN ID: UMIN000008622). |
| Databáze: | OpenAIRE |
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