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Detection of acquired resistance mutation ALK G1202R after treatment with alectinib and response of lorlatinib

  • In the era of personalized medicine, the identification of driver mutations has paved the way towards targeted therapy. With the identification of anaplastic lymphoma kinase (ALK) as an oncogenic driver mutation, ALK rearrangements became druggable by tyrosine kinase inhibitors and, thus, have improved the prognosis for patients. Nevertheless, these approaches are limited by resistances occurring within the first or second year of administering ALK inhibitors. Among the different ALK resistant mutations, G1202R is the most common mutation, located in the kinase domain of the ALK protein resulting in resistance to treatment with the first- and second-generation kinase inhibitors (e.g., crizotinib, ceritinib, brigatenib and alectinib). Conflicting reports exist regarding the efficacy of lorlatinib, a next generation ALK inhibitor. The aim of this study is to access the potential impact of lorlatinib as a second-line treatment for a metastatic progressive NSCLC disease harboring genomic alteration of ALK G1202R, an AKLi-resistant mutation. The case of a patient with advanced lung cancer and the mentioned mutation is described.

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Metadaten
Verfasserangaben:Louisa Hempel, Jakob Molnar, Andreas Gaumann, Sebastian Robert, Josef Scheiber, Axel Kleespies, Kristina Riedmann, Susanne Schreiber, Beate Gandorfer, Armin Piehler, Dirk Hempel
URL:https://doi.org/10.1007/s12254-021-00724-2
Titel des übergeordneten Werkes (Englisch):memo - Magazine of European Medical Oncology
Untertitel (Englisch):A case report
Dokumentart:Artikel (peer reviewed)
Sprache:Englisch
Erscheinungsjahr:2021
Freies Schlagwort / Tag:Molecular diagnostics; NSCLC; Next-generation ALK inhibitor; Next-generation sequencing; Resistance mechanisms
Peer reviewed:Ja
Fakultäten / Organisationseinheiten:Fakultät für Angewandte Gesundheits- und Sozialwissenschaften