Monitoring treatment efficacy and resistance in breast cancer patients via circulating tumor DNA genomic profiling
| العنوان: | Monitoring treatment efficacy and resistance in breast cancer patients via circulating tumor DNA genomic profiling |
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| المؤلفون: | Xiaojia Wang, Junrong Yan, Ziyan Yang, Yabing Zheng, Xue Wu, Wen-Ming Cao, Yang W. Shao, Zhanhong Chen, Tian Sun, Ruoying Yu, Xiying Shao |
| المصدر: | Molecular Genetics & Genomic Medicine, Vol 8, Iss 2, Pp n/a-n/a (2020) Molecular Genetics & Genomic Medicine |
| بيانات النشر: | Wiley, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Oncology, Receptor, ErbB-2, medicine.medical_treatment, Drug resistance, 030105 genetics & heredity, medicine.disease_cause, chemotherapy, Circulating Tumor DNA, Targeted therapy, Antineoplastic Agents, Immunological, Trastuzumab, skin and connective tissue diseases, ERBB2, Genetics (clinical), Mutation, Neurofibromin 1, medicine.diagnostic_test, ErbB Receptors, trastuzumab, Biomarker (medicine), Female, Original Article, medicine.drug, Adult, medicine.medical_specialty, lcsh:QH426-470, Class I Phosphatidylinositol 3-Kinases, Breast Neoplasms, 03 medical and health sciences, Breast cancer, breast cancer, Internal medicine, Biopsy, Biomarkers, Tumor, Genetics, medicine, Humans, Liquid biopsy, Molecular Biology, neoplasms, drug resistance, business.industry, Histone-Lysine N-Methyltransferase, Original Articles, ctDNA, medicine.disease, lcsh:Genetics, 030104 developmental biology, Drug Resistance, Neoplasm, Tumor Suppressor Protein p53, business |
| الوصف: | Background One of the major challenges in managing invasive breast cancer (BC) is the lack of reliable biomarkers to track response. Circulating tumor DNA (ctDNA) from liquid biopsy, as a candidate biomarker, provides a valuable assessment of BC patients. In this retrospective study, we evaluated the utility of ctDNA to reflect the efficacy of treatment and to monitor resistance mechanisms. Methods Targeted next‐generation sequencing (NGS) of 416 cancer‐relevant genes was performed on 41 plasma biopsy samples of 19 HER2+ and 12 HER2‐ BC patients. Longitudinal ctDNA samples were analyzed in three BC patients over the treatment course for detecting acquired mutations. Results In HER2+ BC patients, ERBB2 somatic copy numbers in ctDNA samples were significantly higher in patients progressed on HER2‐targeted therapy than those who were still responding to the treatment. Recurrent acquired mutations were detected in genes including ERBB2, TP53, EGFR, NF1, and SETD2, which may contribute to trastuzumab resistance. In longitudinal analyses, the observed mutation allele frequencies were tracked closely in concordance with treatment responses. A novel ERBB2 p.(Leu869Arg) mutation was acquired in one patient upon resistant to trastuzumab therapy, which was further validated as an oncogenic mutation in vitro and contributed to resistance. In HER2‐ BC patients with chemotherapy resistance, genetic alterations on TP53, PIK3CA, and DNA damage repair genes were frequently observed. Conclusions In summary, ctDNA monitoring, particularly longitudinal analyses, provides valuable insights into the assessment of targeted therapy efficacy and gene alterations underlying trastuzumab resistance and chemotherapy resistance in HER2+ and HER2‐ BC patients, respectively. ctDNA molecular alterations in HER2+ patients developed acquired resistance to trastuzumab and Longitudinal analyses of multiple somatic mutations in ctDNA in patients with acquired resistance to trastuzumab. |
| اللغة: | English |
| تدمد: | 2324-9269 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8bb8954d78984f1000f5dbd8182ca34bTest https://doaj.org/article/860204ae204a497986d88eec577b5261Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....8bb8954d78984f1000f5dbd8182ca34b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23249269 |
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