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Osimertinib in EGFR-Mutant Non-Small Cell Lung Carcinoma: Clinical Activity and Mechanisms of Resistance

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Lung Cancer

Part of the book series: Current Cancer Research ((CUCR))

Abstract

Oncogenic mutations in the epidermal growth factor receptor (EGFR) are identified in a subset of non-small cell lung carcinomas (NSCLC). These alterations lead to constitutive EGFR activation and upregulation of pathways promoting cell survival and proliferation. The development of small molecule inhibitors of EGFR has transformed the care of patients with advanced EGFR-mutant NSCLC. We review here the clinical development and activity of the third-generation EGFR inhibitor osimertinib in the advanced and adjuvant settings. As with other targeted therapies, resistance to osimertinib is common and limits the efficacy of this agent. Here we present an overview of reported acquired resistance mechanisms and potential therapeutic strategies to overcome resistance. The heterogeneity of resistance mechanisms (including secondary EGFR mutations and diverse EGFR-independent alterations) presents a major therapeutic challenge in EGFR-mutant NSCLC.

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Authors and Affiliations

  1. Department of Medicine (Medical Oncology), Yale School of Medicine/Yale Cancer Center, New Haven, CT, USA

    Ashita Talsania, Janie Zhang & Frederick H. Wilson

Authors
  1. Ashita Talsania
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  2. Janie Zhang
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  3. Frederick H. Wilson
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Corresponding author

Correspondence to Frederick H. Wilson .

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Editors and Affiliations

  1. Yale Comprehensive Cancer Center, Yale University, New Haevn, CT, USA

    Anne C. Chiang

  2. Yale Comprehensive Cancer Center, Yale University, New Haevn, CT, USA

    Roy S. Herbst

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Talsania, A., Zhang, J., Wilson, F.H. (2021). Osimertinib in EGFR-Mutant Non-Small Cell Lung Carcinoma: Clinical Activity and Mechanisms of Resistance. In: Chiang, A.C., Herbst, R.S. (eds) Lung Cancer. Current Cancer Research. Humana, Cham. https://doi.org/10.1007/978-3-030-74028-3_4

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  • DOI: https://doi.org/10.1007/978-3-030-74028-3_4

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  • Publisher Name: Humana, Cham

  • Print ISBN: 978-3-030-74027-6

  • Online ISBN: 978-3-030-74028-3

  • eBook Packages: MedicineMedicine (R0)

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