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Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure
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Properties of resistant cells generated from lung cancer cell lines treated with EGFR inhibitors

Gargi Ghosh1, Xiaojun Lian, Stephen J Kron

  • 1Department of Chemical and Biological Engineering, University of Wisconsin, Madison, 53706, USA.

BMC Cancer
|March 22, 2012
PubMed
Abstract

Insights

Targeting epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC) may lead to drug resistance by generating cancer stem cells. These cells exhibit stem cell properties and reduced sensitivity to EGFR inhibitors.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Epidermal growth factor receptor (EGFR) signaling is crucial in non-small cell lung cancer (NSCLC).
  • EGFR inhibitors are effective for a subset of NSCLC patients with somatic EGFR mutations, but resistance eventually develops.
  • Mechanisms of resistance include secondary EGFR mutations (T790M) or MET amplification, with unknown causes in 30-40% of cases.

Purpose of the Study:

  • To investigate the potential development of cancer stem cell-like properties in NSCLC cells upon acquisition of resistance to EGFR inhibitors.
  • To assess the characteristics and drug sensitivity of erlotinib-resistant NSCLC cells.

Main Methods:

  • Generated an erlotinib-resistant NSCLC cell line (H1650-ER1) by continuous exposure to erlotinib.
  • Assessed cancer stem cell-like traits, including stem cell marker expression, self-renewal, differentiation, and tumorigenicity in vitro.

Main Results:

  • The erlotinib-resistant subline (H1650-ER1) exhibited properties consistent with cancer stem cells.
  • These resistant cells demonstrated reduced sensitivity to erlotinib, evidenced by proliferation and tumor sphere formation assays.

Conclusions:

  • Treatment targeting EGFR kinase activity in differentiated cancer cells may inadvertently promote a population of cancer cells with stem cell characteristics.
  • This suggests a potential mechanism for therapeutic resistance in EGFR-mutated NSCLC.

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