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Resistance to EGFR TKIs

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Guide to Targeted Therapies: Treatment Resistance in Lung Cancer

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Abstract

Although epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are effective in patients with EGFR mut+ non-small-cell lung cancer (NSCLC) after an initial response, inevitably all patients become refractory to the therapy after a median time of 8–12 months. Studies of tumor samples from patients at the time of resistance has identified several potential mechanisms of acquired resistance, including: secondsite mutations within the EGFR kinase domain [1,2]; acquired mutations in other oncogenes, such as BRAF and PIK3CA [3,4]; upregulation of other signaling pathways, such as MET, HER2, fibroblast growth factor receptor (FGFR), and AXL [5–10]; and histologic transformation, mainly represented by small cell transformation or epithelial to mesenchymal transition [3]. In addition, approximately 40 % of patients do not respond to the targeted therapy (primary resistance).

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  1. Istituto Toscano Tumori, Ospedale Civile di Livorno, viale Alfieri 36, 57100, Livorno, Italy

    Federico Cappuzzo

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  1. Federico Cappuzzo
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Cappuzzo, F. (2015). Resistance to EGFR TKIs. In: Guide to Targeted Therapies: Treatment Resistance in Lung Cancer. Adis, Cham. https://doi.org/10.1007/978-3-319-20741-4_3

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  • DOI: https://doi.org/10.1007/978-3-319-20741-4_3

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  • Publisher Name: Adis, Cham

  • Print ISBN: 978-3-319-20740-7

  • Online ISBN: 978-3-319-20741-4

  • eBook Packages: MedicineMedicine (R0)

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