Basic mechanisms of resistance to egfr tyrosine kinase egfrinhibitors


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Abstract

Understanding the molecular mechanisms underlying the development of non-small cell lung cancer (NSCLC) has led to revolutionary changes in therapeutic approaches through the emergence of targeted drugs. One of the main directions is the blocking of the epidermal growth factor receptor (EGFR) by EGFR tyrosine kinase inhibitors (TKI) such as gefitinib, erlotinib and apathinib, which have demonstrated an advantage in terms of first-line chemotherapy for advanced EGFR-positive NSCLC. Soon or late, in all patients against the background of therapy with EGFR-TKI, the progression of the disease with median PFS on average 9-13 months develops. Understanding the mechanisms underlying the development of resistance to EGFR-TKI can help in the development of new drugs and therapeutic strategies in order to overcome resistance. The development of the third generation TKI is illustrative of this approach. Drugs of this group effectively influence the T790M mutation, which is the most frequent mechanism of acquired resistance to the first-generation EGFR-TKI. In this article, we will highlight the main mechanisms of primary and secondary resistance to EGFR-TKI in NSCLC with EGFR mutation.

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About the authors

D. D Sakaeva

SBHCI "Republican Clinical Oncological Dispensary" of MH of RB

Email: d_sakaeva@mail.ru
MD, Deputy Chief Physician for Chemotherapy

M. G Gordiev

SAHCI "Republican Clinical Oncological Dispensary" of MH of RT

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