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Updated: Jul 17, 2026

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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PTEN-mediated resistance to epidermal growth factor receptor kinase inhibitors

Ingo K Mellinghoff1, Tim F Cloughesy, Paul S Mischel

  • 1Departments of Molecular and Medical Pharmacology, Neurology, and Pathology and Henry E. Singleton Brain Tumor Program, David Geffen School of Medicine, University of California-Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|January 27, 2007
PubMed

Insights

Loss of the PTEN tumor-suppressor protein can cause resistance to epidermal growth factor receptor tyrosine kinase inhibitors in glioblastoma. Understanding molecular circuitry is key for targeted cancer therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genetics

Background:

  • Molecularly targeted therapies are revolutionizing cancer treatment.
  • Understanding signaling networks is crucial for targeted therapy success.
  • Tumor cell "addiction" to growth-regulating kinases predicts response.

Purpose of the Study:

  • To discuss resistance mechanisms to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs).
  • To highlight the role of tumor-suppressor protein loss in targeted therapy resistance.
  • To examine EGFR-TKI resistance in glioblastoma mediated by PTEN loss.

Main Methods:

  • Review of existing evidence on molecular signaling in cancer.
  • Analysis of clinical data regarding glioblastoma treatment response.
  • Focus on the PTEN tumor-suppressor protein's role in EGFR-TKI resistance.

Main Results:

  • Constitutive kinase mutations can lead to tumor cell "addiction" and initial treatment response.
  • Loss of tumor-suppressor proteins, like PTEN, represents an alternative resistance mechanism.
  • PTEN loss is identified as a mediator of resistance to EGFR-TKIs in glioblastoma.

Conclusions:

  • Clinical response to targeted therapies is influenced by complex molecular circuitry.
  • Loss of PTEN is a significant mechanism of resistance to EGFR-TKIs in glioblastoma.
  • Further research into molecular networks is essential for overcoming targeted therapy resistance.

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