The DOI matches its Crossref record; 45 of the 45 references it cites were found in a registry or an index.
Epithelial versus Mesenchymal Phenotype Determines In vitro Sensitivity and Predicts Clinical Activity of Erlotinib in Lung Cancer Patients
Abstract
Significant improvements in the outcome of non-small cell lung carcinoma (NSCLC) have been reported in patients treated with the epidermal growth factor receptor (EGFR) inhibitor, erlotinib. To discover biomarkers for the enrichment of patients who might benefit from treatment, a pharmacogenomic approach was used to identify gene signatures that may predict erlotinib activity using in vitro model systems. Erlotinib sensitivity in a panel of 42 NSCLC cell lines was determined by EGFR-mediated proliferative potential, EGFR mutations, and/or EGFR gene amplification, thus supporting an underlying biological mechanism of receptor activation. A strong multigene signature indicative of an epithelial to mesenchymal transition (EMT) was identified as a determinant of insensitivity to erlotinib through both supervised and unsupervised gene expression approaches. This observation was further supported by expression analysis of classic EMT marker proteins, including E-cadherin and vimentin. To investigate the clinical relevance of these findings, we examined expression of the epithelial marker E-cadherin by immunohistochemistry on primary tumor samples from subjects enrolled in a randomized NSCLC clinical trial in which erlotinib in combination with chemotherapy previously failed to show clinical activity. The majority (75%) of the 87 subjects tested showed strong E-cadherin staining and exhibited a significantly longer time to progression (hazard ratio, 0.37; log rank P=0.0028) and a nonsignificant trend toward longer survival with erlotinib plus chemotherapy treatment versus chemotherapy alone. These data support a potential role for EMT as a determinant of EGFR activity in NSCLC tumor cells and E-cadherin expression as a novel biomarker predicting clinical activity of the EGFR inhibitor erlotinib in NSCLC patients.
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“In the Tarceva Responses in conjunction with Paclitaxel and Carboplatin (TRIBUTE) trial,38 among patients receiving erlotinib and chemotherapy, time to progression was longer for those with E-cadherin-positive staining.39”
From Mechanisms of resistance to EGFR-targeted drugs: lung cancer (2016) · cites this paper as [39]
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Cites
Cluster analysis and display of genome-wide expression patterns
Eisen, M. B., Spellman, P. T., Brown, P. O., & Botstein, D. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.25.14863 · Cited by 16,184
Lynch, T. J., Bell, D. W., Sordella, R., Gurubhagavatula, S., Okimoto, R. A., Brannigan, B. W., Harris, P. L., Haserlat, S. M., Supko, J. G., Haluska, F. G., et al. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa040938 · Cited by 11,486
EGFR Mutations in Lung Cancer: Correlation with Clinical Response to Gefitinib Therapy
Paez, J. G., Jänne, P. A., Lee, J. C., Tracy, S., Greulich, H., Gabriel, S., Herman, P., Kaye, F. J., Lindeman, N., Boggon, T. J., et al. (2004) · Science · doi:10.1126/science.1099314 · Cited by 9,368
Untangling the ErbB signalling network
Yarden, Y., & Sliwkowski, M. X. (2001) · Nature Reviews Molecular Cell Biology · doi:10.1038/35052073 · Cited by 6,974
Tissue microarrays for high-throughput molecular profiling of tumor specimens
Kononen, J., Bubendorf, L., Kallionimeni, A., Barlund, M. T., Schraml, P., Leighton, S. B., Torhorst, J. K. H., Mihatsch, M. J., Sauter, G., & Kallionimeni, O.-P. (1998) · Nature Medicine · doi:10.1038/nm0798-844 · Cited by 4,101
EGFR Mutation and Resistance of Non–Small-Cell Lung Cancer to Gefitinib
Kobayashi, S., Boggon, T. J., Dayaram, T., Jänne, P. A., Kocher, O., Meyerson, M., Johnson, B. E., Eck, M. J., Tenen, D. G., & Halmos, B. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa044238 · Cited by 3,964
Pao, W., Miller, V. A., Politi, K. A., Riely, G. J., Somwar, R., Zakowski, M. F., Kris, M. G., & Varmus, H. (2005) · PLoS Medicine · doi:10.1371/journal.pmed.0020073 · Cited by 3,527
ERBB receptors and cancer: the complexity of targeted inhibitors
Hynes, N. E., & Lane, H. A. (2005) · Nature reviews. Cancer · doi:10.1038/nrc1609 · Cited by 3,379
Epidermal growth factor-related peptides and their receptors in human malignancies
Salomon, D. S., Brandt, R., Ciardiello, F., & Normanno, N. (1995) · Critical Reviews in Oncology/Hematology · doi:10.1016/1040-8428(94)00144-i · Cited by 2,695
Gefitinib-Sensitizing EGFR Mutations in Lung Cancer Activate Anti-Apoptotic Pathways
Sordella, R., Bell, D. W., Haber, D. A., & Settleman, J. E. (2004) · Science · doi:10.1126/science.1101637 · Cited by 1,605
Cited by
Sorted by citations
Epithelial-Mesenchymal Transitions in Development and Disease
Thiery, J. P., Acloque, H., Huang, R. Y. J., & Nieto, M. A. (2009) · Cell · doi:10.1016/j.cell.2009.11.007 · Cited by 9,931
EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer
Singh, A., & Settleman, J. (2010) · Oncogene · doi:10.1038/onc.2010.215 · Cited by 2,545
Identification of Selective Inhibitors of Cancer Stem Cells by High-Throughput Screening
Gupta, P. B., Önder, T. T., Jiang, G., Tao, K. X., Kuperwasser, C., Weinberg, R. A., & Lander, E. S. (2009) · Cell · doi:10.1016/j.cell.2009.06.034 · Cited by 2,429
Herbst, R. S., Heymach, J. V., & Lippman, S. M. (2008) · New England Journal of Medicine · doi:10.1056/nejmra0802714 · Cited by 2,435
Epidermal Growth Factor Receptor Cell Proliferation Signaling Pathways
Wee, P., & Wang, Z. (2017) · Cancers · doi:10.3390/cancers9050052 · Cited by 2,027
Metadata
- Authors
- Yauch, R. L., Januario, T., Eberhard, D. A., Cavet, G., Zhu, W., Fu, L., Pham, T. Q., Soriano, R., Stinson, J., Seshagiri, S., Modrusan, Z., Lin, C.-Y., O'Neill, V., & Amler, L. C.
- Affiliations
- Genentech (US)
- 5BioOncology, Genentech, Inc., South San Francisco, California
- Venue
- Clinical Cancer Research
- Published
- 2005-12-15
- Volume
- 11
- Issue
- 24
- Pages
- 8686-8698
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- OpenAlex
- W2111599976
- Cited by
- 495
- References
- 45
- Citations by year
- 2026: 4 · 2025: 6 · 2023: 12 · 2022: 7 · 2021: 15 · 2020: 15 · 2019: 15 · 2018: 21 · 2017: 41 · 2016: 29 · 2015: 27 · 2014: 35 · 2013: 50 · 2012: 36
- FWCI
- 21.12
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Food and Drug Administration
- Division of Materials Research
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- erlotinib, non-small cell lung cancer, epithelial-mesenchymal transition, E-cadherin, EGFR inhibitors, predictive biomarkers, pharmacogenomics, EGFR mutation, EGFR amplification, vimentin, time to progression, combination chemotherapy
- MeSH terms
- Erlotinib Hydrochloride, Antineoplastic Agents, Carcinoma, Non-Small-Cell Lung, Epithelium, Gene Amplification, Humans, Immunohistochemistry, Lung Neoplasms, Mesoderm, Mutation, Pharmacogenetics, Phenotype, Quinazolines, Biomarkers, Tumor, Vimentin, Cadherins, Treatment Outcome, Drug Resistance, Neoplasm, Oligonucleotide Array Sequence Analysis, Cell Line, Tumor, Protein Kinase Inhibitors, Cell Proliferation, Genes, Neoplasm, ErbB Receptors
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