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      Ceritinib Treatment for Carcinomatous Meningitis with a Secondary Mutation at I1171T in Anaplastic Lymphoma Kinase

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          Abstract

          The mechanisms underlying anaplastic lymphoma kinase (ALK) resistance have not been well investigated in clinical practice. We herein report the case of a lung cancer patient with carcinomatous meningitis who had an ALK I1171T resistance mutation revealed by direct DNA sequencing of the cerebrospinal fluid after treatment with cytotoxic chemotherapy, crizotinib, and alectinib. I1171T is considered to be sensitive to ceritinib. Although ceritinib was not effective initially, we chose ceritinib again after whole-brain radiotherapy and ventriculoperitoneal shunting. Although the response duration was short, spinal magnetic resonance imaging revealed a marked response. The identification of an acquired ALK resistance mutation will aid in choosing the optimum sequence therapy.

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          Targeting ALK: Precision Medicine Takes on Drug Resistance.

          Anaplastic lymphoma kinase (ALK) is a validated molecular target in several ALK-rearranged malignancies, including non-small cell lung cancer. However, the clinical benefit of targeting ALK using tyrosine kinase inhibitors (TKI) is almost universally limited by the emergence of drug resistance. Diverse mechanisms of resistance to ALK TKIs have now been discovered, and these basic mechanisms are informing the development of novel therapeutic strategies to overcome resistance in the clinic. In this review, we summarize the current successes and challenges of targeting ALK.
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            Two novel ALK mutations mediate acquired resistance to the next-generation ALK inhibitor alectinib.

            The first-generation ALK tyrosine kinase inhibitor (TKI) crizotinib is a standard therapy for patients with ALK-rearranged non-small cell lung cancer (NSCLC). Several next-generation ALK-TKIs have entered the clinic and have shown promising activity in crizotinib-resistant patients. As patients still relapse even on these next-generation ALK-TKIs, we examined mechanisms of resistance to the next-generation ALK-TKI alectinib and potential strategies to overcome this resistance.
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              Leptomeningeal Metastases in Patients with NSCLC with EGFR Mutations.

              Leptomeningeal metastases (LM) have increased in patients with NSCLC, and prognostic factors and outcomes for LM with EGFR gene mutations have not been well studied.
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                Author and article information

                Journal
                Intern Med
                Intern. Med
                Internal Medicine
                The Japanese Society of Internal Medicine
                0918-2918
                1349-7235
                6 June 2018
                1 November 2018
                : 57
                : 21
                : 3153-3155
                Affiliations
                [1 ]Division of Respiratory Medicine, Chiba Cancer Center, Japan
                [2 ]Division of Neurological Surgery, Chiba Cancer Center, Japan
                [3 ]Division of Translational Genomics, Chiba Cancer Center, Japan
                Author notes

                Correspondence to Dr. Hironori Ashinuma, hashinuma@ 123456chiba-cc.jp

                Article
                10.2169/internalmedicine.0397-17
                6262718
                29877262
                a7b29870-bcfc-4b6d-ae15-15ca04b2694c
                Copyright © 2018 by The Japanese Society of Internal Medicine

                The Internal Medicine is an Open Access journal distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. To view the details of this license, please visit ( https://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 24 October 2017
                : 22 March 2018
                Categories
                Case Report

                alk,alectinib,ceritinib,i1171t,csf
                alk, alectinib, ceritinib, i1171t, csf

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