IMR Press / FBL / Volume 16 / Issue 5 / DOI: 10.2741/3823

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
EGFR tyrosine kinase inhibitors and multidrug resistance: perspectives
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1 Dipartimento Farmacochimico, Universita degli Studi di Bari, A Moro, via Orabona, 4, 70125 Bari, Italy. colabufo@farmchim.uniba.it

Academic Editor: Amalia Azzariti

Front. Biosci. (Landmark Ed) 2011, 16(5), 1811–1823; https://doi.org/10.2741/3823
Published: 1 January 2011
Abstract

Aim of present review is to provide an evidence-based update of mechanisms responsible for the onset of resistance to drug therapy by EGFR inhibitors, particularly with regards to TKIs. Among ABC transporters involved in MDR, P-glycoprotein and BCRP have been considered the pumps responsible for TKIs treatment failure. Moreover, two subtypes of EGFR mutations have been described: mutations of the exons coding for tyrosine kinase domain (18 to 21) and truncating mutations (exons 2 to 7) that involve downstream effectors such as MAPK, PI3K/Akt, STAT. The first group of mutations can be considered as a hallmark of NSCLC and are responsible for the failure of TKIs while the second group of mutations leads to resistance. The strategies to overcome MDR and to bypass the kinase domain mutations have been addressed. Finally, for some first generation TKIs some perspectives as radiotracers for PET/SPECT diagnosis in tumor displaying P-gp and BCRP overexpression have been suggested.

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