Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
MET Amplification Leads to Gefitinib Resistance in Lung Cancer by Activating ERBB3 Signaling
Jeffrey A. Engelman,1,2,3Kreshnik Zejnullahu,4,5Tetsuya Mitsudomi,6Youngchul Song,2,3Courtney Hyland,7Joon Oh Park,4,5Neal Lindeman,7Christopher-Michael Gale,3Xiaojun Zhao,5James Christensen,8Takayuki Kosaka,6Alison J. Holmes,4,5Andrew M. Rogers,5Federico Cappuzzo,9Tony Mok,10Charles Lee,7Bruce E. Johnson,4,5Lewis C. Cantley,2,3Pasi A. Jänne4,5*
The epidermal growth factor receptor (EGFR) kinase inhibitorsgefitinib and erlotinib are effective treatments for lung cancerswith EGFR activating mutations, but these tumors invariablydevelop drug resistance. Here, we describe a gefitinib-sensitivelung cancer cell line that developed resistance to gefitinibas a result of focal amplification of the MET proto-oncogene.inhibition of MET signaling in these cells restored their sensitivityto gefitinib. MET amplification was detected in 4 of 18 (22%)lung cancer specimens that had developed resistance to gefitinibor erlotinib. We find that amplification of MET causes gefitinibresistance by driving ERBB3 (HER3)–dependent activationof PI3K, a pathway thought to be specific to EGFR/ERBB familyreceptors. Thus, we propose that MET amplification may promotedrug resistance in other ERBB-driven cancers as well.
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. 6 Department of Thoracic Surgery, Aichi Cancer Center Hospital, Nagoya 464-8681, Japan. 7 Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA. 8 Pfizer Global Research and Development, Department of Research Pharmacology, La Jolla Laboratories, La Jolla, CA 92121, USA. 9 Istituto Clinico Humanitas, Department on Hematology-Oncology, Rozzano 20089, Italy. 10 Department of Clinical Oncology, Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China.
* To whom correspondence should be addressed. E-mail: pjanne{at}partners.org
The editors suggest the following Related Resources on Science sites:
In Science Signaling
EDITORS' CHOICE
Paula A. Kiberstis (22 May 2007) Sci. STKE2007 (387), tw180.
[DOI: 10.1126/stke.3872007tw180] |Abstract »
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Reciprocal Regulation of c-Src and STAT3 in Non-Small Cell Lung Cancer.
L. A. Byers, B. Sen, B. Saigal, L. Diao, J. Wang, M. Nanjundan, T. Cascone, G. B. Mills, J. V. Heymach, and F. M. Johnson (2009)
Clin. Cancer Res.
15, 6852-6861
|Abstract »|Full Text »|PDF »
Crosstalk to Stromal Fibroblasts Induces Resistance of Lung Cancer to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors.
W. Wang, Q. Li, T. Yamada, K. Matsumoto, I. Matsumoto, M. Oda, G. Watanabe, Y. Kayano, Y. Nishioka, S. Sone, et al. (2009)
Clin. Cancer Res.
15, 6630-6638
|Abstract »|Full Text »|PDF »
Identifying genotype-dependent efficacy of single and combined PI3K- and MAPK-pathway inhibition in cancer.
M. L. Sos, S. Fischer, R. Ullrich, M. Peifer, J. M. Heuckmann, M. Koker, S. Heynck, I. Stuckrath, J. Weiss, F. Fischer, et al. (2009)
PNAS
106, 18351-18356
|Abstract »|Full Text »|PDF »
Inhibition of Tumor Cell Growth, Invasion, and Metastasis by EXEL-2880 (XL880, GSK1363089), a Novel Inhibitor of HGF and VEGF Receptor Tyrosine Kinases.
F. Qian, S. Engst, K. Yamaguchi, P. Yu, K.-A. Won, L. Mock, T. Lou, J. Tan, C. Li, D. Tam, et al. (2009)
Cancer Res.
69, 8009-8016
|Abstract »|Full Text »|PDF »
HGF/Met signalling promotes PGE2 biogenesis via regulation of COX-2 and 15-PGDH expression in colorectal cancer cells.
A. E. Moore, A. Greenhough, H. R. Roberts, D. J. Hicks, H. A. Patsos, A. C. Williams, and C. Paraskeva (2009)
Carcinogenesis
30, 1796-1804
|Abstract »|Full Text »|PDF »
Treatment after the Failure of Gefitinib in Patients with Advanced or Recurrent Non-small Cell Lung Cancer.
R. MARUYAMA, H. WATAYA, T. SETO, and Y. ICHINOSE (2009)
Anticancer Res
29, 4217-4221
|Abstract »|Full Text »|PDF »
The Role of MET Activation in Determining the Sensitivity to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors.
J. K. Rho, Y. J. Choi, J. K. Lee, B.-Y. Ryoo, I. I. Na, S. H. Yang, S. S. Lee, C. H. Kim, Y. D. Yoo, and J. C. Lee (2009)
Mol. Cancer Res.
7, 1736-1743
|Abstract »|Full Text »|PDF »
Treatment of Medulloblastoma with Hedgehog Pathway Inhibitor GDC-0449.
C. M. Rudin, C. L. Hann, J. Laterra, R. L. Yauch, C. A. Callahan, L. Fu, T. Holcomb, J. Stinson, S. E. Gould, B. Coleman, et al. (2009)
N. Engl. J. Med.
361, 1173-1178
|Abstract »|Full Text »|PDF »
Ethnic Differences and Functional Analysis of MET Mutations in Lung Cancer.
S. Krishnaswamy, R. Kanteti, J. S. Duke-Cohan, S. Loganathan, W. Liu, P. C. Ma, M. Sattler, P. A. Singleton, N. Ramnath, F. Innocenti, et al. (2009)
Clin. Cancer Res.
15, 5714-5723
|Abstract »|Full Text »|PDF »
Stratified phase II trial of cetuximab in patients with recurrent high-grade glioma.
B. Neyns, J. Sadones, E. Joosens, F. Bouttens, L. Verbeke, J.-F. Baurain, L. D'Hondt, T. Strauven, C. Chaskis, P. In't Veld, et al. (2009)
Ann. Onc.
20, 1596-1603
|Abstract »|Full Text »|PDF »
Novel Mechanism of Lapatinib Resistance in HER2-Positive Breast Tumor Cells: Activation of AXL.
L. Liu, J. Greger, H. Shi, Y. Liu, J. Greshock, R. Annan, W. Halsey, G. M. Sathe, A.-M. Martin, and T. M. Gilmer (2009)
Cancer Res.
69, 6871-6878
|Abstract »|Full Text »|PDF »
Chemopreventive Effects of Gefitinib on Nonsmoking-Related Lung Tumorigenesis in Activating Epidermal Growth Factor Receptor Transgenic Mice.
K. Ohashi, N. Takigawa, M. Osawa, E. Ichihara, H. Takeda, T. Kubo, S. Hirano, T. Yoshino, M. Takata, M. Tanimoto, et al. (2009)
Cancer Res.
69, 7088-7095
|Abstract »|Full Text »|PDF »
Impact of Epidermal Growth Factor Receptor and KRAS Mutations on Clinical Outcomes in Previously Untreated Non-Small Cell Lung Cancer Patients: Results of an Online Tumor Registry of Clinical Trials.
D. M. Jackman, V. A. Miller, L.-A. Cioffredi, B. Y. Yeap, P. A. Janne, G. J. Riely, M. G. Ruiz, G. Giaccone, L. V. Sequist, and B. E. Johnson (2009)
Clin. Cancer Res.
15, 5267-5273
|Abstract »|Full Text »|PDF »
Angioinhibitory Action of NK4 Involves Impaired Extracellular Assembly of Fibronectin Mediated by Perlecan-NK4 Association.
K. Sakai, T. Nakamura, K. Matsumoto, and T. Nakamura (2009)
J. Biol. Chem.
284, 22491-22499
|Abstract »|Full Text »|PDF »
Met induces diverse mammary carcinomas in mice and is associated with human basal breast cancer.
C. R. Graveel, J. D. DeGroot, Y. Su, J. Koeman, K. Dykema, S. Leung, J. Snider, S. R. Davies, P. J. Swiatek, S. Cottingham, et al. (2009)
PNAS
106, 12909-12914
|Abstract »|Full Text »|PDF »
High-throughput molecular analysis in lung cancer: insights into biology and potential clinical applications.
S. Ocak, M. L. Sos, R. K. Thomas, and P. P. Massion (2009)
Eur. Respir. J.
34, 489-506
|Abstract »|Full Text »|PDF »
The Green Tea Polyphenol EGCG Potentiates the Antiproliferative Activity of c-Met and Epidermal Growth Factor Receptor Inhibitors in Non-small Cell Lung Cancer Cells.
S. A. Milligan, P. Burke, D. T. Coleman, R. L. Bigelow, J. J. Steffan, J. L. Carroll, B. J. Williams, and J. A. Cardelli (2009)
Clin. Cancer Res.
15, 4885-4894
|Abstract »|Full Text »|PDF »
MiR-21 is an EGFR-regulated anti-apoptotic factor in lung cancer in never-smokers.
M. Seike, A. Goto, T. Okano, E. D. Bowman, A. J. Schetter, I. Horikawa, E. A. Mathe, J. Jen, P. Yang, H. Sugimura, et al. (2009)
PNAS
106, 12085-12090
|Abstract »|Full Text »|PDF »
Combined inhibition of MET and EGFR suppresses proliferation of malignant mesothelioma cells.
K. Kawaguchi, H. Murakami, T. Taniguchi, M. Fujii, S. Kawata, T. Fukui, Y. Kondo, H. Osada, N. Usami, K. Yokoi, et al. (2009)
Carcinogenesis
30, 1097-1105
|Abstract »|Full Text »|PDF »
EGFRvIII and c-Met pathway inhibitors synergize against PTEN-null/EGFRvIII+ glioblastoma xenografts.
B. Lal, C. R. Goodwin, Y. Sang, C. A. Foss, K. Cornet, S. Muzamil, M. G. Pomper, J. Kim, and J. Laterra (2009)
Mol. Cancer Ther.
8, 1751-1760
|Abstract »|Full Text »|PDF »
Therapeutically Targeting ErbB3: A Key Node in Ligand-Induced Activation of the ErbB Receptor-PI3K Axis.
B. Schoeberl, E. A. Pace, J. B. Fitzgerald, B. D. Harms, L. Xu, L. Nie, B. Linggi, A. Kalra, V. Paragas, R. Bukhalid, et al. (2009)
Science Signaling
2, ra31
|Abstract »|Full Text »|PDF »
Effects of Vandetanib on Lung Adenocarcinoma Cells Harboring Epidermal Growth Factor Receptor T790M Mutation In vivo.
E. Ichihara, K. Ohashi, N. Takigawa, M. Osawa, A. Ogino, M. Tanimoto, and K. Kiura (2009)
Cancer Res.
69, 5091-5098
|Abstract »|Full Text »|PDF »
CUDC-305, a Novel Synthetic HSP90 Inhibitor with Unique Pharmacologic Properties for Cancer Therapy.
R. Bao, C.-J. Lai, H. Qu, D. Wang, L. Yin, B. Zifcak, R. Atoyan, J. Wang, M. Samson, J. Forrester, et al. (2009)
Clin. Cancer Res.
15, 4046-4057
|Abstract »|Full Text »|PDF »
Toward Noninvasive Genomic Screening of Lung Cancer Patients.
L. V. Sequist, J. A. Engelman, and T. J. Lynch (2009)
J. Clin. Oncol.
27, 2589-2591
|Full Text »|PDF »
Combination Effect between Bortezomib and Tumor Necrosis Factor {alpha} on Gefitinib-resistant Non-small Cell Lung Cancer Cell Lines.
S. KUSUMOTO, T. SUGIYAMA, K. ANDO, T. HOSAKA, H. ISHIDA, T. SHIRAI, T. YAMAOKA, K. OKUDA, T. HIROSE, T. OHNISHI, et al. (2009)
Anticancer Res
29, 2315-2322
|Abstract »|Full Text »|PDF »
Src Promotes Survival and Invasion of Lung Cancers with Epidermal Growth Factor Receptor Abnormalities and Is a Potential Candidate for Molecular-Targeted Therapy.
E. L.-H. Leung, I. Y.-S. Tam, V. P.-C. Tin, D. T.-T. Chua, A. D.-L. Sihoe, L.-C. Cheng, J. C.-M. Ho, L.-P. Chung, and M. P. Wong (2009)
Mol. Cancer Res.
7, 923-932
|Abstract »|Full Text »|PDF »
HGF and c-Met Participate in Paracrine Tumorigenic Pathways in Head and Neck Squamous Cell Cancer.
L. M. Knowles, L. P. Stabile, A. M. Egloff, M. E. Rothstein, S. M. Thomas, C. T. Gubish, E. C. Lerner, R. R. Seethala, S. Suzuki, K. M. Quesnelle, et al. (2009)
Clin. Cancer Res.
15, 3740-3750
|Abstract »|Full Text »|PDF »
Decorin is a novel antagonistic ligand of the Met receptor.
S. Goldoni, A. Humphries, A. Nystrom, S. Sattar, R. T. Owens, D. J. McQuillan, K. Ireton, and R. V. Iozzo (2009)
J. Cell Biol.
185, 743-754
|Abstract »|Full Text »|PDF »
Heregulin Regulates Prolactinoma Gene Expression.
G. Vlotides, O. Cooper, Y.-H. Chen, S.-G. Ren, Y. Greenman, and S. Melmed (2009)
Cancer Res.
69, 4209-4216
|Abstract »|Full Text »|PDF »
Combined Vascular Endothelial Growth Factor Receptor and Epidermal Growth Factor Receptor (EGFR) Blockade Inhibits Tumor Growth in Xenograft Models of EGFR Inhibitor Resistance.
G. N. Naumov, M. B. Nilsson, T. Cascone, A. Briggs, O. Straume, L. A. Akslen, E. Lifshits, L. A. Byers, L. Xu, H.-k. Wu, et al. (2009)
Clin. Cancer Res.
15, 3484-3494
|Abstract »|Full Text »|PDF »
Src-Induced Cisplatin Resistance Mediated by Cell-to-Cell Communication.
E. Peterson-Roth, C. M. Brdlik, and P. M. Glazer (2009)
Cancer Res.
69, 3619-3624
|Abstract »|Full Text »|PDF »
Noninvasive Detection of EGFR T790M in Gefitinib or Erlotinib Resistant Non-Small Cell Lung Cancer.
Y. Kuang, A. Rogers, B. Y. Yeap, L. Wang, M. Makrigiorgos, K. Vetrand, S. Thiede, R. J. Distel, and P. A. Janne (2009)
Clin. Cancer Res.
15, 2630-2636
|Abstract »|Full Text »|PDF »
Increased MET Gene Copy Number Negatively Affects Survival of Surgically Resected Non-Small-Cell Lung Cancer Patients.
F. Cappuzzo, A. Marchetti, M. Skokan, E. Rossi, S. Gajapathy, L. Felicioni, M. del Grammastro, M. G. Sciarrotta, F. Buttitta, M. Incarbone, et al. (2009)
J. Clin. Oncol.
27, 1667-1674
|Abstract »|Full Text »|PDF »
The MET Receptor Tyrosine Kinase Is a Potential Novel Therapeutic Target for Head and Neck Squamous Cell Carcinoma.
T. Y. Seiwert, R. Jagadeeswaran, L. Faoro, V. Janamanchi, V. Nallasura, M. El Dinali, S. Yala, R. Kanteti, E. E.W. Cohen, M. W. Lingen, et al. (2009)
Cancer Res.
69, 3021-3031
|Abstract »|Full Text »|PDF »
Is erlotinib really active after failure of gefitinib in advanced non-small-cell lung cancer patients?.
E. Vasile, C. Tibaldi, and A. Falcone (2009)
Ann. Onc.
20, 790-791
|Full Text »|PDF »
Novel Therapeutic Inhibitors of the c-Met Signaling Pathway in Cancer.
J. P. Eder, G. F. Vande Woude, S. A. Boerner, and P. M. LoRusso (2009)
Clin. Cancer Res.
15, 2207-2214
|Abstract »|Full Text »|PDF »
Combined Inhibition of the VEGFR and EGFR Signaling Pathways in the Treatment of NSCLC.
Single-Molecule Detection of Epidermal Growth Factor Receptor Mutations in Plasma by Microfluidics Digital PCR in Non-Small Cell Lung Cancer Patients.
T. K.F. Yung, K.C. A. Chan, T. S.K. Mok, J. Tong, K.-F. To, and Y.M. D. Lo (2009)
Clin. Cancer Res.
15, 2076-2084
|Abstract »|Full Text »|PDF »
Growth Factors Outside of the Platelet-derived Growth Factor (PDGF) Family Employ Reactive Oxygen Species/Src Family Kinases to Activate PDGF Receptor {alpha} and Thereby Promote Proliferation and Survival of Cells.
Establishment and Characterization of a Model of Acquired Resistance to Epidermal Growth Factor Receptor Targeting Agents in Human Cancer Cells.
S. Benavente, S. Huang, E. A. Armstrong, A. Chi, K.-T. Hsu, D. L. Wheeler, and P. M. Harari (2009)
Clin. Cancer Res.
15, 1585-1592
|Abstract »|Full Text »|PDF »
Mutations and Response to Epidermal Growth Factor Receptor Inhibitors.
P. Laurent-Puig, A. Lievre, and H. Blons (2009)
Clin. Cancer Res.
15, 1133-1139
|Abstract »|Full Text »|PDF »
EGFR-TKI and lung adenocarcinoma with CNS relapse: interest of molecular follow-up.
A-M. Ruppert, M. Beau-Faller, A. Neuville, E. Guerin, A-C. Voegeli, B. Mennecier, M. Legrain, A. Molard, M-Y. Jeung, M-P. Gaub, et al. (2009)
Eur. Respir. J.
33, 436-440
|Abstract »|Full Text »|PDF »
MET increased gene copy number and primary resistance to gefitinib therapy in non-small-cell lung cancer patients.
F. Cappuzzo, P. A. Janne, M. Skokan, G. Finocchiaro, E. Rossi, C. Ligorio, P. A. Zucali, L. Terracciano, L. Toschi, M. Roncalli, et al. (2009)
Ann. Onc.
20, 298-304
|Abstract »|Full Text »|PDF »
Addition of S-1 to the Epidermal Growth Factor Receptor Inhibitor Gefitinib Overcomes Gefitinib Resistance in Non-small cell Lung Cancer Cell Lines with MET Amplification.
T. Okabe, I. Okamoto, S. Tsukioka, J. Uchida, E. Hatashita, Y. Yamada, T. Yoshida, K. Nishio, M. Fukuoka, P. A. Janne, et al. (2009)
Clin. Cancer Res.
15, 907-913
|Abstract »|Full Text »|PDF »
Functional Analysis of Epidermal Growth Factor Receptor (EGFR) Mutations and Potential Implications for EGFR Targeted Therapy.
R. K. Kancha, N. von Bubnoff, C. Peschel, and J. Duyster (2009)
Clin. Cancer Res.
15, 460-467
|Abstract »|Full Text »|PDF »
Inhibition of fatty acid synthase by luteolin post-transcriptionally down-regulates c-Met expression independent of proteosomal/lysosomal degradation.
D. T. Coleman, R. Bigelow, and J. A. Cardelli (2009)
Mol. Cancer Ther.
8, 214-224
|Abstract »|Full Text »|PDF »
Fibroblast Growth Factor (FGF) and FGF Receptor-Mediated Autocrine Signaling in Non-Small-Cell Lung Cancer Cells.
L. Marek, K. E. Ware, A. Fritzsche, P. Hercule, W. R. Helton, J. E. Smith, L. A. McDermott, C. D. Coldren, R. A. Nemenoff, D. T. Merrick, et al. (2009)
Mol. Pharmacol.
75, 196-207
|Abstract »|Full Text »|PDF »
A mouse model for EML4-ALK-positive lung cancer.
M. Soda, S. Takada, K. Takeuchi, Y. L. Choi, M. Enomoto, T. Ueno, H. Haruta, T. Hamada, Y. Yamashita, Y. Ishikawa, et al. (2008)
PNAS
105, 19893-19897
|Abstract »|Full Text »|PDF »
Phase II study of erlotinib as a salvage treatment for non-small-cell lung cancer patients after failure of gefitinib treatment.
D. H. Lee, S.-W. Kim, C. Suh, D. H. Yoon, E. J. Yi, and J.-S. Lee (2008)
Ann. Onc.
19, 2039-2042
|Abstract »|Full Text »|PDF »
Genetic Predictors of MEK Dependence in Non-Small Cell Lung Cancer.
C. A. Pratilas, A. J. Hanrahan, E. Halilovic, Y. Persaud, J. Soh, D. Chitale, H. Shigematsu, H. Yamamoto, A. Sawai, M. Janakiraman, et al. (2008)
Cancer Res.
68, 9375-9383
|Abstract »|Full Text »|PDF »
Hepatocyte Growth Factor Induces Gefitinib Resistance of Lung Adenocarcinoma with Epidermal Growth Factor Receptor-Activating Mutations.
S. Yano, W. Wang, Q. Li, K. Matsumoto, H. Sakurama, T. Nakamura, H. Ogino, S. Kakiuchi, M. Hanibuchi, Y. Nishioka, et al. (2008)
Cancer Res.
68, 9479-9487
|Abstract »|Full Text »|PDF »
Acquired Resistance to Epidermal Growth Factor Receptor Kinase Inhibitors Associated with a Novel T854A Mutation in a Patient with EGFR-Mutant Lung Adenocarcinoma.
J. Bean, G. J. Riely, M. Balak, J. L. Marks, M. Ladanyi, V. A. Miller, and W. Pao (2008)
Clin. Cancer Res.
14, 7519-7525
|Abstract »|Full Text »|PDF »
Reduced Erlotinib Sensitivity of Epidermal Growth Factor Receptor-Mutant Non-Small Cell Lung Cancer following Cisplatin Exposure: A Cell Culture Model of Second-line Erlotinib Treatment.
T. M. Chin, M. P. Quinlan, A. Singh, L. V. Sequist, T. J. Lynch, D. A. Haber, S. V. Sharma, and J. Settleman (2008)
Clin. Cancer Res.
14, 6867-6876
|Abstract »|Full Text »|PDF »
Effects of Erlotinib in EGFR Mutated Non-Small Cell Lung Cancers with Resistance to Gefitinib.
D. B. Costa, K.-S. H. Nguyen, B. C. Cho, L. V. Sequist, D. M. Jackman, G. J. Riely, B. Y. Yeap, B. Halmos, J. H. Kim, P. A. Janne, et al. (2008)
Clin. Cancer Res.
14, 7060-7067
|Abstract »|Full Text »|PDF »
HER kinase activation confers resistance to MET tyrosine kinase inhibition in MET oncogene-addicted gastric cancer cells.
T. Bachleitner-Hofmann, M. Y. Sun, C.-T. Chen, L. Tang, L. Song, Z. Zeng, M. Shah, J. G. Christensen, N. Rosen, D. B. Solit, et al. (2008)
Mol. Cancer Ther.
7, 3499-3508
|Abstract »|Full Text »|PDF »
Establishment of Patient-Derived Non-Small Cell Lung Cancer Xenografts as Models for the Identification of Predictive Biomarkers.
I. Fichtner, J. Rolff, R. Soong, J. Hoffmann, S. Hammer, A. Sommer, M. Becker, and J. Merk (2008)
Clin. Cancer Res.
14, 6456-6468
|Abstract »|Full Text »|PDF »
Inhibition of Hsp90 activates osteoclast c-Src signaling and promotes growth of prostate carcinoma cells in bone.
A. Yano, S. Tsutsumi, S. Soga, M.-J. Lee, J. Trepel, H. Osada, and L. Neckers (2008)
PNAS
105, 15541-15546
|Abstract »|Full Text »|PDF »
Chemical and Pathway Proteomics: Powerful Tools for Oncology Drug Discovery and Personalized Health Care.
U. Kruse, M. Bantscheff, G. Drewes, and C. Hopf (2008)
Mol. Cell. Proteomics
7, 1887-1901
|Abstract »|Full Text »|PDF »
Laser Capture Microdissection and Protein Microarray Analysis of Human Non-small Cell Lung Cancer: Differential Epidermal Growth Factor Receptor (EGPR) Phosphorylation Events Associated with Mutated EGFR Compared with Wild Type.
A. J. VanMeter, A. S. Rodriguez, E. D. Bowman, J. Jen, C. C. Harris, J. Deng, V. S. Calvert, A. Silvestri, C. Fredolini, V. Chandhoke, et al. (2008)
Mol. Cell. Proteomics
7, 1902-1924
|Abstract »|Full Text »|PDF »
Human epidermal growth factor receptor (HER-1:HER-3) Fc-mediated heterodimer has broad antiproliferative activity in vitro and in human tumor xenografts.
J. Sarup, P. Jin, L. Turin, X. Bai, M. Beryt, C. Brdlik, J. N. Higaki, B. Jorgensen, F. W. Lau, P. Lindley, et al. (2008)
Mol. Cancer Ther.
7, 3223-3236
|Abstract »|Full Text »|PDF »
Single-Agent and Combination Therapeutic Strategies to Inhibit Hepatocyte Growth Factor/MET Signaling in Cancer.
R. S. Herbst, J. V. Heymach, and S. M. Lippman (2008)
N. Engl. J. Med.
359, 1367-1380
|Full Text »|PDF »
Transforming Growth Factor {beta} Engages TACE and ErbB3 To Activate Phosphatidylinositol-3 Kinase/Akt in ErbB2-Overexpressing Breast Cancer and Desensitizes Cells to Trastuzumab.
S. E. Wang, B. Xiang, M. Guix, M. G. Olivares, J. Parker, C. H. Chung, A. Pandiella, and C. L. Arteaga (2008)
Mol. Cell. Biol.
28, 5605-5620
|Abstract »|Full Text »|PDF »
Role of cMET expression in non-small-cell lung cancer patients treated with EGFR tyrosine kinase inhibitors.
P. A. Zucali, M. G. Ruiz, E. Giovannetti, A. Destro, M. Varella-Garcia, K. Floor, G. L. Ceresoli, J. A. Rodriguez, I. Garassino, P. Comoglio, et al. (2008)
Ann. Onc.
19, 1605-1612
|Abstract »|Full Text »|PDF »
Gefitinib in Advanced Non-Small Cell Lung Cancer: Does It Deserve a Second Chance?.
Identification of a Novel Recepteur d'Origine Nantais/c-Met Small-Molecule Kinase Inhibitor with Antitumor Activity In vivo.
Y. Zhang, P. J. Kaplan-Lefko, K. Rex, Y. Yang, J. Moriguchi, T. Osgood, B. Mattson, A. Coxon, M. Reese, T.-S. Kim, et al. (2008)
Cancer Res.
68, 6680-6687
|Abstract »|Full Text »|PDF »
Gefitinib Induction of In vivo Detectable Signals by Bcl-2/Bcl-xL Modulation of Inositol Trisphosphate Receptor Type 3.
A. Zannetti, F. Iommelli, R. Fonti, A. Papaccioli, J. Sommella, A. Lettieri, G. Pirozzi, R. Bianco, G. Tortora, M. Salvatore, et al. (2008)
Clin. Cancer Res.
14, 5209-5219
|Abstract »|Full Text »|PDF »
Vascular Endothelial Growth Factor Receptor-1 Contributes to Resistance to Anti-Epidermal Growth Factor Receptor Drugs in Human Cancer Cells.
R. Bianco, R. Rosa, V. Damiano, G. Daniele, T. Gelardi, S. Garofalo, V. Tarallo, S. De Falco, D. Melisi, R. Benelli, et al. (2008)
Clin. Cancer Res.
14, 5069-5080
|Abstract »|Full Text »|PDF »
Chromosomal Abnormalities in Cancer.
S. Frohling and H. Dohner (2008)
N. Engl. J. Med.
359, 722-734
|Full Text »|PDF »
Improved tumor targeting of anti-epidermal growth factor receptor Nanobodies through albumin binding: taking advantage of modular Nanobody technology.
B. M. Tijink, T. Laeremans, M. Budde, M. S.-v. Walsum, T. Dreier, H. J. de Haard, C. R. Leemans, and G. A.M.S. van Dongen (2008)
Mol. Cancer Ther.
7, 2288-2297
|Abstract »|Full Text »|PDF »
Case 23-2008 -- A 26-Year-Old Man with Back Pain and a Mass in the Lung.
L. V. Sequist, J. E. Settleman, J. B. Ackman, and A. J. Iafrate (2008)
N. Engl. J. Med.
359, 405-414
|Full Text »|PDF »
Detection of Mutations in EGFR in Circulating Lung-Cancer Cells.
S. Maheswaran, L. V. Sequist, S. Nagrath, L. Ulkus, B. Brannigan, C. V. Collura, E. Inserra, S. Diederichs, A. J. Iafrate, D. W. Bell, et al. (2008)
N. Engl. J. Med.
359, 366-377
|Abstract »|Full Text »|PDF »
Erlotinib in a Patient With Acute Myelogenous Leukemia and Concomitant Non-Small-Cell Lung Cancer.
V. Pitini, C. Arrigo, and G. Altavilla (2008)
J. Clin. Oncol.
26, 3645-3646
|Full Text »|PDF »
T. Shimamura, D. Li, H. Ji, H. J. Haringsma, E. Liniker, C. L. Borgman, A. M. Lowell, Y. Minami, K. McNamara, S. A. Perera, et al. (2008)
Cancer Res.
68, 5827-5838
|Abstract »|Full Text »|PDF »
Class 1A PI3K regulates vessel integrity during development and tumorigenesis.
T. L. Yuan, H. S. Choi, A. Matsui, C. Benes, E. Lifshits, J. Luo, J. V. Frangioni, and L. C. Cantley (2008)
PNAS
105, 9739-9744
|Abstract »|Full Text »|PDF »
Therapeutic targeting of human hepatocyte growth factor with a single neutralizing monoclonal antibody reduces lung tumorigenesis.
L. P. Stabile, M. E. Rothstein, P. Keohavong, J. Jin, J. Yin, S. R. Land, S. Dacic, T. M. Luong, K. J. Kim, A. M. Dulak, et al. (2008)
Mol. Cancer Ther.
7, 1913-1922
|Abstract »|Full Text »|PDF »
MicroRNA miR-199a* Regulates the MET Proto-oncogene and the Downstream Extracellular Signal-regulated Kinase 2 (ERK2).
S. Kim, U. J. Lee, M. N. Kim, E.-J. Lee, J. Y. Kim, M. Y. Lee, S. Choung, Y. J. Kim, and Y.-C. Choi (2008)
J. Biol. Chem.
283, 18158-18166
|Abstract »|Full Text »|PDF »
Elevated CRAF as a Potential Mechanism of Acquired Resistance to BRAF Inhibition in Melanoma.
C. Montagut, S. V. Sharma, T. Shioda, U. McDermott, M. Ulman, L. E. Ulkus, D. Dias-Santagata, H. Stubbs, D. Y. Lee, A. Singh, et al. (2008)
Cancer Res.
68, 4853-4861
|Abstract »|Full Text »|PDF »
Specific EGFR Mutations Predict Treatment Outcome of Stage IIIB/IV Patients With Chemotherapy-Naive Non-Small-Cell Lung Cancer Receiving First-Line Gefitinib Monotherapy.
J. C. Montero, R. Rodriguez-Barrueco, A. Ocana, E. Diaz-Rodriguez, A. Esparis-Ogando, and A. Pandiella (2008)
Clin. Cancer Res.
14, 3237-3241
|Abstract »|Full Text »|PDF »
First-Line Gefitinib in Patients With Advanced Non-Small-Cell Lung Cancer Harboring Somatic EGFR Mutations.
L. V. Sequist, R. G. Martins, D. Spigel, S. M. Grunberg, A. Spira, P. A. Janne, V. A. Joshi, D. McCollum, T. L. Evans, A. Muzikansky, et al. (2008)
J. Clin. Oncol.
26, 2442-2449
|Abstract »|Full Text »|PDF »
Molecular Selection of Patients for First-Line Treatment of Advanced Non-Small-Cell Lung Cancer With Epidermal Growth Factor Inhibitors: Not Quite Ready for Prime Time.
F. A. Shepherd (2008)
J. Clin. Oncol.
26, 2426-2427
|Full Text »|PDF »
Inhibition of N-Linked Glycosylation Disrupts Receptor Tyrosine Kinase Signaling in Tumor Cells.
J. N. Contessa, M. S. Bhojani, H. H. Freeze, A. Rehemtulla, and T. S. Lawrence (2008)
Cancer Res.
68, 3803-3809
|Abstract »|Full Text »|PDF »
Mechanisms of Acquired Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Non-Small Cell Lung Cancer.
Met and c-Src Cooperate to Compensate for Loss of Epidermal Growth Factor Receptor Kinase Activity in Breast Cancer Cells.
K. L. Mueller, L. A. Hunter, S. P. Ethier, and J. L. Boerner (2008)
Cancer Res.
68, 3314-3322
|Abstract »|Full Text »|PDF »
EXEL-7647 Inhibits Mutant Forms of ErbB2 Associated with Lapatinib Resistance and Neoplastic Transformation.
T. Trowe, S. Boukouvala, K. Calkins, R. E. Cutler Jr., R. Fong, R. Funke, S. B. Gendreau, Y. D. Kim, N. Miller, J. R. Woolfrey, et al. (2008)
Clin. Cancer Res.
14, 2465-2475
|Abstract »|Full Text »|PDF »
