American Association for Cancer Research
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00085472can084055-sup-supplemental_figure.pdf (656.59 kB)

Supplementary Figure from PTEN Loss Contributes to Erlotinib Resistance in EGFR-Mutant Lung Cancer by Activation of Akt and EGFR

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posted on 2023-03-30, 19:01 authored by Martin L. Sos, Mirjam Koker, Barbara A. Weir, Stefanie Heynck, Rosalia Rabinovsky, Thomas Zander, Jens M. Seeger, Jonathan Weiss, Florian Fischer, Peter Frommolt, Kathrin Michel, Martin Peifer, Craig Mermel, Luc Girard, Michael Peyton, Adi F. Gazdar, John D. Minna, Levi A. Garraway, Hamid Kashkar, William Pao, Matthew Meyerson, Roman K. Thomas
Supplementary Figure from PTEN Loss Contributes to Erlotinib Resistance in EGFR-Mutant Lung Cancer by Activation of Akt and EGFR

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ARTICLE ABSTRACT

Clinical resistance to epidermal growth factor receptor (EGFR) inhibition in lung cancer has been linked to the emergence of the EGFR T790M resistance mutation or amplification of MET. Additional mechanisms contributing to EGFR inhibitor resistance remain elusive. By applying combined analyses of gene expression, copy number, and biochemical analyses of EGFR inhibitor responsiveness, we identified homozygous loss of PTEN to segregate EGFR-dependent and EGFR-independent cells. We show that in EGFR-dependent cells, PTEN loss partially uncouples mutant EGFR from downstream signaling and activates EGFR, thereby contributing to erlotinib resistance. The clinical relevance of our findings is supported by the observation of PTEN loss in 1 out of 24 primary EGFR-mutant non–small cell lung cancer (NSCLC) tumors. These results suggest a novel resistance mechanism in EGFR-mutant NSCLC involving PTEN loss. [Cancer Res 2009;69(8):3256–61]

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