Resistance to EGFR inhibitors in non-small cell lung cancer: clinical management and future perspectives

Publication date: Available online 6 February 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Chiara Tomasello, Cinzia Baldessari, Martina Napolitano, Giulia Orsi, Giulia Grizzi, Federica Bertolini, Fausto Barbieri, Stefano Cascinu
In the last few years, the development of targeted therapies for non-small cell lung cancer (NSCLC) expressing oncogenic driver mutations (e.g. EGFR) has changed the clinical management and the survival outcomes of this specific minority of patients. Several phase III trials demonstrated the superiority of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) over chemotherapy in EGFR-mutant NSCLC patients. However, in the vast majority of cases EGFR TKIs lose their clinical activity within 8–12 months. Many genetic aberrations have been described as possible mechanisms of EGFR TKIs acquired resistance and can be clustered in four main sub-groups: 1. Development of secondary EGFR mutations; 2. Activation of parallel signaling pathways; 3. Histological transformation; 4. Activation of downstream signaling pathways.



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