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      Transformation to small-cell carcinoma as an acquired resistance mechanism to AZD9291: A case report

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          Abstract

          AZD9291, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), benefits patients with T790M mutant non-small-cell lung cancer who fail treatment with first-generation EGFR TKIs. Acquisition of resistance to AZD9291 occurs inevitable and mechanisms need to be explored. We reported an advanced lung adenocarcinoma female with EGFR exon19 deletion treated on AZD9291 after failure of erlotinib and chemotherapy. Disease progressed again after 6 months treatment of AZD9291 with hepatic metastasis. Re-biopsy of the hepatic lesion showed histopathology transformation to small cell lung cancer, which harbored EGFR exon19 deletion. Therefore, small cell carcinoma transformation is one of potential resistance mechanisms to AZD9291 and regimen for small cell carcinoma may be one of the treatment options.

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          Most cited references6

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          Mechanisms of Acquired Resistance to AZD9291: A Mutation-Selective, Irreversible EGFR Inhibitor.

          AZD9291, a third-generation and mutation-selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), is active against patients with EGFR-mutant non-small-cell lung cancer (NSCLC) who failed prior treatment with EGFR TKIs. However, acquired resistance to AZD9291 is inevitable. In this study, we identified the mechanisms of acquired resistance to AZD9291 in EGFR-mutant NSCLC.
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            Two Cases of Small Cell Lung Cancer Transformation from EGFR Mutant Adenocarcinoma During AZD9291 Treatment.

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              Transformation to small-cell lung cancer following treatment with EGFR tyrosine kinase inhibitors in a patient with lung adenocarcinoma.

              We report the case of a 52-year-old woman with lung adenocarcinoma treated with EGFR tyrosine kinase inhibitor (TKI) therapy. After disease progression, histological examination of a secondary biopsy specimen revealed small-cell lung cancer (SCLC) that was sensitive to standard SCLC treatment. Tumor markers, including ProGRP and NSE, were elevated. Transformation to SCLC is a mechanism for acquired resistance to EGFR-TKI therapy. Secondary biopsy is important for evaluation of genetic and histological changes and selection of appropriate treatment. Furthermore, ProGRP and NSE may be useful for early detection of SCLC transformation in cases resistant to EGFR-TKI therapy.
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                Author and article information

                Journal
                Oncotarget
                Oncotarget
                Oncotarget
                ImpactJ
                Oncotarget
                Impact Journals LLC
                1949-2553
                14 March 2017
                4 January 2017
                : 8
                : 11
                : 18609-18614
                Affiliations
                1 Department of Oncology, Beijing Hospital, National Center of Gerontology, Beijing, China
                2 Department of Pathology, Beijing Hospital, National Center of Gerontology, Beijing, China
                Author notes
                Correspondence to: Lin Li, lilin_51@ 123456hotmail.com
                Article
                14506
                10.18632/oncotarget.14506
                5392352
                28061471
                b1cd7cb0-b5ed-4d9a-908d-7e2f5a3ee07f
                Copyright: © 2017 Li et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 11 October 2016
                : 27 December 2016
                Categories
                Case Report

                Oncology & Radiotherapy
                nsclc,egfr-tki,azd9291,acquired resistance,transformation
                Oncology & Radiotherapy
                nsclc, egfr-tki, azd9291, acquired resistance, transformation

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