MET Amplification Leads to Gefitinib Resistance in Lung Cancer by Activating ERBB3 Signaling-Reference-Cited by-同舟云学术

MET Amplification Leads to Gefitinib Resistance in Lung Cancer by Activating ERBB3 Signaling

Published:2007-05-18 Issue:5827 Volume:316 Page:1039-1043
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Engelman Jeffrey A.¹²³⁴⁵,Zejnullahu Kreshnik¹²³⁴⁵,Mitsudomi Tetsuya¹²³⁴⁵,Song Youngchul¹²³⁴⁵,Hyland Courtney¹²³⁴⁵,Park Joon Oh¹²³⁴⁵,Lindeman Neal¹²³⁴⁵,Gale Christopher-Michael¹²³⁴⁵,Zhao Xiaojun¹²³⁴⁵,Christensen James¹²³⁴⁵,Kosaka Takayuki¹²³⁴⁵,Holmes Alison J.¹²³⁴⁵,Rogers Andrew M.¹²³⁴⁵,Cappuzzo Federico¹²³⁴⁵,Mok Tony¹²³⁴⁵,Lee Charles¹²³⁴⁵,Johnson Bruce E.¹²³⁴⁵,Cantley Lewis C.¹²³⁴⁵,Jänne Pasi A.¹²³⁴⁵

Affiliation:

1. Massachusetts General Hospital Cancer Center, Boston, MA 02114, USA.

2. Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.

3. Department of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA.

4. Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.

5. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.

Abstract

The epidermal growth factor receptor (EGFR) kinase inhibitors gefitinib and erlotinib are effective treatments for lung cancers with EGFR activating mutations, but these tumors invariably develop drug resistance. Here, we describe a gefitinib-sensitive lung cancer cell line that developed resistance to gefitinib as a result of focal amplification of the MET proto-oncogene. inhibition of MET signaling in these cells restored their sensitivity to gefitinib. MET amplification was detected in 4 of 18 (22%) lung cancer specimens that had developed resistance to gefitinib or erlotinib. We find that amplification of MET causes gefitinib resistance by driving ERBB3 (HER3)–dependent activation of PI3K, a pathway thought to be specific to EGFR/ERBB family receptors. Thus, we propose that MET amplification may promote drug resistance in other ERBB-driven cancers as well.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference24 articles.

1. Activity of a Specific Inhibitor of the BCR-ABL Tyrosine Kinase in the Blast Crisis of Chronic Myeloid Leukemia and Acute Lymphoblastic Leukemia with the Philadelphia Chromosome

2. Efficacy and Safety of Imatinib Mesylate in Advanced Gastrointestinal Stromal Tumors

3. EGFR Mutations in Lung Cancer: Correlation with Clinical Response to Gefitinib Therapy

4. Activating Mutations in the Epidermal Growth Factor Receptor Underlying Responsiveness of Non–Small-Cell Lung Cancer to Gefitinib

5. Analysis of Epidermal Growth Factor Receptor Gene Mutation in Patients with Non–Small Cell Lung Cancer and Acquired Resistance to Gefitinib

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