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

Critical Reviews in Oncology/hematology
Chiara TomaselloStefano Cascinu

Abstract

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. In this review we will describe the molecular alterations underlying each of these EGFR TKIs resistance mechanisms, focusing on the currently available and future therapeutic strategies to overcome these phenomena.

Citations

Jan 17, 2019·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·Rashmi R Shah, Devron R Shah
Aug 15, 2019·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Vanita NoronhaKumar Prabhash
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Dec 11, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Nele Van Der SteenPatrick Pauwels
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Feb 9, 2021·European Journal of Medicinal Chemistry·Qi LiangJianyou Shi
Aug 29, 2020·The International Journal of Biochemistry & Cell Biology·Sara Teixeira Soares MotaThaise Gonçalves Araújo
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