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. 2012:2012:817297.
doi: 10.1155/2012/817297. Epub 2012 Aug 29.

Mechanisms of Resistance to Epidermal Growth Factor Receptor Inhibitors and Novel Therapeutic Strategies to Overcome Resistance in NSCLC Patients

Luping Lin  1 , Trever G Bivona
Affiliations

Mechanisms of Resistance to Epidermal Growth Factor Receptor Inhibitors and Novel Therapeutic Strategies to Overcome Resistance in NSCLC Patients

Luping Lin et al. Chemother Res Pract. 2012.

Abstract

The epidermal growth factor receptor (EGFR) is a well-characterized oncogene that is frequently activated by somatic kinase domain mutations in non-small cell lung cancer (NSCLC). EGFR TKIs are effective therapies for NSCLC patients whose tumors harbor an EGFR activating mutation. However, EGFR TKI treatment is not curative in patients because of both primary and secondary treatment resistance. Studies over the last decade have identified mechanisms that drive primary and secondary resistance to EGFR TKI treatment. The elucidation of mechanisms of resistance to EGFR TKI treatment provides a basis for the development of therapeutic strategies to overcome resistance and enhance outcomes in NSCLC patients. In this paper, we summarize the mechanisms of resistance to EGFR TKIs that have been identified to date and discusses potential therapeutic strategies to overcome EGFR TKI resistance in NSCLC patients.

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Figures

Figure 1
Figure 1
Mechanisms of resistance to EGFR TKIs and multiple strategies to overcome resistance in EGFR mutant lung cancer. EGFR signals through the RAS/RAF/MEK/ERK and PI3K/AKT pathways to promote cellular proliferation and survival. Crosstalk of other receptor tyrosine kinase confers resistance to EGFR TKIs by activation of both MAPK and AKT signaling. The FAS/NFκB signaling arm downstream of FAS death receptor also contributes to resistance to EGFR TKIs. Available targeted agents that act against pathways that drive EGFR TKI resistance and that may overcome resistance to EGFR TKIs in appropriately selected lung cancer patients are shown.
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