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Relevance of MET activation and genetic alterations of KRAS and E-cadherin for cetuximab sensitivity of gastric cancer cell lines

  • Original Paper
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Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

The therapeutic activity of the epidermal growth factor receptor (EGFR)-directed monoclonal antibody cetuximab in gastric cancer is currently being investigated. Reliable biomarkers for the identification of patients who are likely to benefit from the treatment are not available. The aim of the study was to examine the drug sensitivity of five gastric cancer cell lines towards cetuximab as a single agent and to establish predictive markers for chemosensitivity in this cell culture model. The effect of a combination of cetuximab with chemotherapy was compared between a sensitive and a nonsensitive cell line.

Methods

EGFR expression, activation and localisation, the presence and subcellular localisation of the cell adhesion molecule E-cadherin as well as MET activation were examined by Western blot analysis, flow cytometry and immunofluorescence staining. Cells were treated with varying concentrations of cetuximab and cisplatin and 5-fluorouracil in tumour-relevant concentrations. The biological endpoint was cell viability, which was measured by XTT cell proliferation assay. Response to treatment was evaluated using statistical methods.

Results

We assessed the activity of cetuximab in five gastric cancer cell lines (AGS, KATOIII, MKN1, MKN28 and MKN45). The viability of two cell lines, MKN1 and MKN28, was significantly reduced by cetuximab treatment. High EGFR expression and low levels of receptor activation were associated with cetuximab responsiveness. MET activation as well as mutations of KRAS and CDH1 (gene encoding E-cadherin) was associated with cetuximab resistance.

Conclusion

These data indicate that our examinations may be clinically relevant, and the candidate markers should therefore be tested in clinical studies.

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Abbreviations

Ab:

Antibody

DAPI:

4,6-Diamidino-2-phenylindole dihydrochloride

DMEM:

Dulbecco’s modified Eagle’s medium

ECS:

Enhanced chemoluminescence system

EGFR:

Epidermal growth factor receptor

FC:

Flow cytometry

IU:

International units

PBS:

Phosphate-buffered saline

RTK:

Receptor tyrosine kinase

SD:

Standard deviation

WB:

Western blot

References

  • Adams GP, Weiner LM (2005) Monoclonal antibody therapy of cancer. Nat Biotechnol 23(9):1147–1157. doi:nbt1137[pii]10.1038/nbt1137

    Article  PubMed  CAS  Google Scholar 

  • Agarwal S, Zerillo C, Kolmakova J, Christensen JG, Harris LN, Rimm DL, Digiovanna MP, Stern DF (2009) Association of constitutively activated hepatocyte growth factor receptor (Met) with resistance to a dual EGFR/Her2 inhibitor in non-small-cell lung cancer cells. Br J Cancer 100(6):941–949. doi:6604937[pii]10.1038/sj.bjc.6604937

    Article  PubMed  CAS  Google Scholar 

  • Bachleitner-Hofmann T, Sun MY, Chen CT, Tang L, Song L, Zeng Z, Shah M, Christensen JG, Rosen N, Solit DB, Weiser MR (2008) HER kinase activation confers resistance to MET tyrosine kinase inhibition in MET oncogene-addicted gastric cancer cells. Mol Cancer Ther 7(11):3499–3508. doi:1535-7163.MCT-08-0374[pii]10.1158/1535-7163.MCT-08-0374

    Article  PubMed  CAS  Google Scholar 

  • Bardelli A, Siena S (2010) Molecular mechanisms of resistance to cetuximab and panitumumab in colorectal cancer. J Clin Oncol 28(7):1254–1261

    Article  PubMed  CAS  Google Scholar 

  • Baselga J, Pfister D, Cooper MR, Cohen R, Burtness B, Bos M, D’Andrea G, Seidman A, Norton L, Gunnett K, Falcey J, Anderson V, Waksal H, Mendelsohn J (2000) Phase I studies of anti-epidermal growth factor receptor chimeric antibody C225 alone and in combination with cisplatin. J Clin Oncol 18(4):904–914

    PubMed  CAS  Google Scholar 

  • Becker KF, Atkinson MJ, Reich U, Becker I, Nekarda H, Siewert JR, Hofler H (1994) E-cadherin gene mutations provide clues to diffuse type gastric carcinomas. Cancer Res 54(14):3845–3852

    PubMed  CAS  Google Scholar 

  • Benavente S, Huang S, Armstrong EA, Chi A, Hsu KT, Wheeler DL, Harari PM (2009) Establishment and characterization of a model of acquired resistance to epidermal growth factor receptor targeting agents in human cancer cells. Clin Cancer Res 15(5):1585–1592

    Article  PubMed  CAS  Google Scholar 

  • Bertotti A, Bracco C, Girolami F, Torti D, Gastaldi S, Galimi F, Medico E, Elvin P, Comoglio PM, Trusolino L (2010) Inhibition of Src impairs the growth of met-addicted gastric tumors. Clin Cancer Res 16(15):3933–3943. doi:1078-0432.CCR-10-0106[pii]10.1158/1078-0432.CCR-10-0106

    Article  PubMed  CAS  Google Scholar 

  • Berx G, Becker KF, Hofler H, van Roy F (1998) Mutations of the human E-cadherin (CDH1) gene. Hum Mutat 12(4):226–237

    Article  PubMed  CAS  Google Scholar 

  • Black PC, Brown GA, Inamoto T, Shrader M, Arora A, Siefker-Radtke AO, Adam L, Theodorescu D, Wu X, Munsell MF, Bar-Eli M, McConkey DJ, Dinney CP (2008) Sensitivity to epidermal growth factor receptor inhibitor requires E-cadherin expression in urothelial carcinoma cells. Clin Cancer Res 14(5):1478–1486

    Article  PubMed  CAS  Google Scholar 

  • Boyd MR, Paull KD (1995) Some practical considerations and applications of the national cancer institute in vitro anticancer drug discovery screen. Drug Develop Res 34:91–109

    Article  CAS  Google Scholar 

  • Bremm A, Walch A, Fuchs M, Mages J, Duyster J, Keller G, Hermannstadter C, Becker KF, Rauser S, Langer R, von Weyhern CH, Hofler H, Luber B (2008) Enhanced activation of epidermal growth factor receptor caused by tumor-derived E-cadherin mutations. Cancer Res 68(3):707–714. doi:68/3/707[pii]10.1158/0008-5472.CAN-07-1588

    Article  PubMed  CAS  Google Scholar 

  • Cappuzzo F, Varella-Garcia M, Finocchiaro G, Skokan M, Gajapathy S, Carnaghi C, Rimassa L, Rossi E, Ligorio C, Di Tommaso L, Holmes AJ, Toschi L, Tallini G, Destro A, Roncalli M, Santoro A, Janne PA (2008) Primary resistance to cetuximab therapy in EGFR FISH-positive colorectal cancer patients. Br J Cancer 99(1):83–89. doi:6604439[pii]10.1038/sj.bjc.6604439

    Article  PubMed  CAS  Google Scholar 

  • Chung KY, Shia J, Kemeny NE, Shah M, Schwartz GK, Tse A, Hamilton A, Pan D, Schrag D, Schwartz L, Klimstra DS, Fridman D, Kelsen DP, Saltz LB (2005) Cetuximab shows activity in colorectal cancer patients with tumors that do not express the epidermal growth factor receptor by immunohistochemistry. J Clin Oncol 23(9):1803–1810

    Article  PubMed  CAS  Google Scholar 

  • Ciardiello F, Tortora G (2008) EGFR antagonists in cancer treatment. N Engl J Med 358(11):1160–1174

    Article  PubMed  CAS  Google Scholar 

  • Dietel M, Bals U, Schaefer B, Herzig I, Arps H, Zabel M (1993) In vitro prediction of cytostatic drug resistance in primary cell cultures of solid malignant tumours. Eur J Cancer 29A(3):416–420

    Article  PubMed  CAS  Google Scholar 

  • Engelman JA, Janne PA (2008) Mechanisms of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer. Clin Cancer Res 14(10):2895–2899. doi:14/10/2895[pii]10.1158/1078-0432.CCR-07-2248

    Article  PubMed  Google Scholar 

  • Engelman JA, Settleman J (2008) Acquired resistance to tyrosine kinase inhibitors during cancer therapy. Curr Opin Genet Dev 18(1):73–79. doi:S0959-437X(08)00008-7[pii]10.1016/j.gde.2008.01.004

    Article  PubMed  CAS  Google Scholar 

  • Engelman JA, Zejnullahu K, Mitsudomi T, Song Y, Hyland C, Park JO, Lindeman N, Gale CM, Zhao X, Christensen J, Kosaka T, Holmes AJ, Rogers AM, Cappuzzo F, Mok T, Lee C, Johnson BE, Cantley LC, Janne PA (2007) MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science 316(5827):1039–1043. doi:1141478[pii]10.1126/science.1141478

    Article  PubMed  CAS  Google Scholar 

  • Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM (2010) Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 127:2893–2917. doi:10.1002/ijc.25516

    Article  PubMed  CAS  Google Scholar 

  • Frixen UH, Behrens J, Sachs M, Eberle G, Voss B, Warda A, Lochner D, Birchmeier W (1991) E-cadherin-mediated cell–cell adhesion prevents invasiveness of human carcinoma cells. J Cell Biol 113(1):173–185

    Article  PubMed  CAS  Google Scholar 

  • Fuchs BC, Fujii T, Dorfman JD, Goodwin JM, Zhu AX, Lanuti M, Tanabe KK (2008) Epithelial-to-mesenchymal transition and integrin-linked kinase mediate sensitivity to epidermal growth factor receptor inhibition in human hepatoma cells. Cancer Res 68(7):2391–2399

    Article  PubMed  CAS  Google Scholar 

  • Gamboa-Dominguez A, Dominguez-Fonseca C, Quintanilla-Martinez L, Reyes-Gutierrez E, Green D, Angeles–Angeles A, Busch R, Hermannstadter C, Nahrig J, Becker KF, Becker I, Hofler H, Fend F, Luber B (2004) Epidermal growth factor receptor expression correlates with poor survival in gastric adenocarcinoma from Mexican patients: a multivariate analysis using a standardized immunohistochemical detection system. Mod Pathol 17(5):579–587

    Article  PubMed  CAS  Google Scholar 

  • Guo A, Villen J, Kornhauser J, Lee KA, Stokes MP, Rikova K, Possemato A, Nardone J, Innocenti G, Wetzel R, Wang Y, MacNeill J, Mitchell J, Gygi SP, Rush J, Polakiewicz RD, Comb MJ (2008) Signaling networks assembled by oncogenic EGFR and c-Met. Proc Natl Acad Sci USA 105(2):692–697. doi:0707270105[pii]10.1073/pnas.0707270105

    Article  PubMed  CAS  Google Scholar 

  • Han SW, Oh DY, Im SA, Park SR, Lee KW, Song HS, Lee NS, Lee KH, Choi IS, Lee MH, Kim MA, Kim WH, Bang YJ, Kim TY (2009) Phase II study and biomarker analysis of cetuximab combined with modified FOLFOX6 in advanced gastric cancer. Br J Cancer 100(2):298–304

    Article  PubMed  CAS  Google Scholar 

  • Hara M, Nakanishi H, Tsujimura K, Matsui M, Yatabe Y, Manabe T, Tatematsu M (2008) Interleukin-2 potentiation of cetuximab antitumor activity for epidermal growth factor receptor-overexpressing gastric cancer xenografts through antibody-dependent cellular cytotoxicity. Cancer Sci 99(7):1471–1478. doi:CAS821[pii]10.1111/j.1349-7006.2008.00821.x

    Article  PubMed  CAS  Google Scholar 

  • Inno A, Salvatore MD, Cenci T, Martini M, Orlandi A, Strippoli A, Ferrara AM, Bagala C, Cassano A, Larocca LM, Barone C (2011) Is there a role for IGF1R and c-MET pathways in resistance to cetuximab in metastatic colorectal cancer? Clin Colorect Cancer. doi:S1533-0028(11)00030-2 [pii] 10.1016/j.clcc.2011.03.028

  • Jhawer M, Goel S, Wilson AJ, Montagna C, Ling YH, Byun DS, Nasser S, Arango D, Shin J, Klampfer L, Augenlicht LH, Soler RP, Mariadason JM (2008) PIK3CA mutation/PTEN expression status predicts response of colon cancer cells to the epidermal growth factor receptor inhibitor cetuximab. Cancer Res 68(6):1953–1961

    Article  PubMed  CAS  Google Scholar 

  • Keller G, Vogelsang H, Becker I, Plaschke S, Ott K, Suriano G, Mateus AR, Seruca R, Biedermann K, Huntsman D, Doring C, Holinski-Feder E, Neutzling A, Siewert JR, Hofler H (2004) Germline mutations of the E-cadherin(CDH1) and TP53 genes, rather than of RUNX3 and HPP1, contribute to genetic predisposition in German gastric cancer patients. J Med Genet 41(6):e89

    Article  PubMed  CAS  Google Scholar 

  • Kim JW, Kim HP, Im SA, Kang S, Hur HS, Yoon YK, Oh DY, Kim JH, Lee DS, Kim TY, Bang YJ (2008) The growth inhibitory effect of lapatinib, a dual inhibitor of EGFR and HER2 tyrosine kinase, in gastric cancer cell lines. Cancer Lett 272(2):296–306. doi:S0304-3835(08)00582-X[pii]10.1016/j.canlet.2008.07.018

    Article  PubMed  CAS  Google Scholar 

  • Krumbach R, Schuler J, Hofmann M, Giesemann T, Fiebig HH, Beckers T (2011) Primary resistance to cetuximab in a panel of patient-derived tumour xenograft models: activation of MET as one mechanism for drug resistance. Eur J Cancer 47(8):1231–1243. doi:S0959-8049(10)01208-6[pii]10.1016/j.ejca.2010.12.019

    Article  PubMed  CAS  Google Scholar 

  • Liska D, Chen CT, Bachleitner-Hofmann T, Christensen JG, Weiser MR (2011) HGF rescues colorectal cancer cells from EGFR inhibition via MET activation. Clin Cancer Res 17(3):472–482. doi:1078-0432.CCR-10-0568[pii]10.1158/1078-0432.CCR-10-0568

    Article  PubMed  CAS  Google Scholar 

  • Liu X, Guo WJ, Zhang XW, Cai X, Tian S, Li J (2011) Cetuximab enhances the activities of irinotecan on gastric cancer cell lines through downregulating the EGFR pathway upregulated by irinotecan. Cancer Chemother Pharmacol. doi:10.1007/s00280-011-1559-2

  • Lordick F, Luber B, Lorenzen S, Hegewisch-Becker S, Folprecht G, Woll E, Decker T, Endlicher E, Rothling N, Schuster T, Keller G, Fend F, Peschel C (2010) Cetuximab plus oxaliplatin/leucovorin/5-fluorouracil in first-line metastatic gastric cancer: a phase II study of the Arbeitsgemeinschaft Internistische Onkologie (AIO). Br J Cancer 102(3):500–505

    Article  PubMed  CAS  Google Scholar 

  • Luber B, Deplazes J, Keller G, Walch A, Rauser S, Eichmann M, Langer R, Höfler H, Hegewisch-Becker S, Folprecht G, Wöll E, Decker T, Endlicher E, Lorenzen S, Fend F, Peschel C, Lordick F (2011) Biomarker analysis of cetuximab plus oxaliplatin/leucovorin/5-fluorouracil in first-line metastatic gastric and oesophago-gastric junction cancer: results from a phase II trial of the Arbeitsgemeinschaft Internistische Onkologie (AIO). BMC Cancer, in press

  • Luo FR, Yang Z, Dong H, Camuso A, McGlinchey K, Fager K, Flefleh C, Kan D, Inigo I, Castaneda S, Rose WC, Kramer RA, Wild R, Lee FY (2005) Correlation of pharmacokinetics with the antitumor activity of Cetuximab in nude mice bearing the GEO human colon carcinoma xenograft. Cancer Chemother Pharmacol 56(5):455–464. doi:10.1007/s00280-005-1022-3

    Article  PubMed  CAS  Google Scholar 

  • Mateus AR, Seruca R, Machado JC, Keller G, Oliveira MJ, Suriano G, Luber B (2007) EGFR regulates RhoA-GTP dependent cell motility in E-cadherin mutant cells. Hum Mol Genet 16(13):1639–1647

    Article  PubMed  CAS  Google Scholar 

  • McDermott U, Pusapati RV, Christensen JG, Gray NS, Settleman J (2010) Acquired resistance of non-small cell lung cancer cells to MET kinase inhibition is mediated by a switch to epidermal growth factor receptor dependency. Cancer Res 70(4):1625–1634. doi:0008-5472.CAN-09-3620[pii]10.1158/0008-5472.CAN-09-3620

    Article  PubMed  CAS  Google Scholar 

  • Moehler M, Mueller A, Trarbach T, Lordick F, Seufferlein T, Kubicka S, Geissler M, Schwarz S, Galle PR, Kanzler S (2010) Cetuximab with irinotecan, folinic acid and 5-fluorouracil as first-line treatment in advanced gastroesophageal cancer: a prospective multi-center biomarker-oriented phase II study. Ann Oncol 22:1358–1366 Epub 2010 Nov 30

    Article  PubMed  Google Scholar 

  • Nakagawa M, Fukata M, Yamaga M, Itoh N, Kaibuchi K (2001) Recruitment and activation of Rac1 by the formation of E-cadherin-mediated cell–cell adhesion sites. J Cell Sci 114(Pt 10):1829–1838

    PubMed  CAS  Google Scholar 

  • Nikolova DA, Asangani IA, Nelson LD, Hughes DP, Siwak DR, Mills GB, Harms A, Buchholz E, Pilz LR, Manegold C, Allgayer H (2009) Cetuximab Attenuates Metastasis and u-PAR Expression in Non-Small Cell Lung Cancer: u-PAR and E-Cadherin are Novel Biomarkers of Cetuximab Sensitivity. Cancer Res 69:2461–2470 Epub 2009 Mar 10

    Article  PubMed  CAS  Google Scholar 

  • Oda T, Kanai Y, Oyama T, Yoshiura K, Shimoyama Y, Birchmeier W, Sugimura T, Hirohashi S (1994) E-cadherin gene mutations in human gastric carcinoma cell lines. Proc Natl Acad Sci USA 91(5):1858–1862

    Article  PubMed  CAS  Google Scholar 

  • Oliveira C, Seruca R, Caldas C (2003) Genetic screening for hereditary diffuse gastric cancer. Expert Rev Mol Diagn 3(2):201–215

    Article  PubMed  CAS  Google Scholar 

  • Paull KD, Shoemaker RH, Hodes L, Monks A, Scudiero DA, Rubinstein L, Plowman J, Boyd MR (1989) Display and analysis of patterns of differential activity of drugs against human tumor cell lines: development of mean graph and COMPARE algorithm. J Natl Cancer Inst 81(14):1088–1092

    Article  PubMed  CAS  Google Scholar 

  • Pinto C, Di Fabio F, Siena S, Cascinu S, Rojas Llimpe FL, Ceccarelli C, Mutri V, Giannetta L, Giaquinta S, Funaioli C, Berardi R, Longobardi C, Piana E, Martoni AA (2007) Phase II study of cetuximab in combination with FOLFIRI in patients with untreated advanced gastric or gastroesophageal junction adenocarcinoma (FOLCETUX study). Ann Oncol 18(3):510–517

    Article  PubMed  CAS  Google Scholar 

  • Pinto C, Di Fabio F, Barone C, Siena S, Falcone A, Cascinu S, Rojas Llimpe FL, Stella G, Schinzari G, Artale S, Mutri V, Giaquinta S, Giannetta L, Bardelli A, Martoni AA (2009) Phase II study of cetuximab in combination with cisplatin and docetaxel in patients with untreated advanced gastric or gastro-oesophageal junction adenocarcinoma (DOCETUX study). Br J Cancer 101(8):1261–1268

    Article  PubMed  CAS  Google Scholar 

  • Qian X, Karpova T, Sheppard AM, McNally J, Lowy DR (2004) E-cadherin-mediated adhesion inhibits ligand-dependent activation of diverse receptor tyrosine kinases. EMBO J 23(8):1739–1748

    Article  PubMed  CAS  Google Scholar 

  • Robert F, Ezekiel MP, Spencer SA, Meredith RF, Bonner JA, Khazaeli MB, Saleh MN, Carey D, LoBuglio AF, Wheeler RH, Cooper MR, Waksal HW (2001) Phase I study of anti–epidermal growth factor receptor antibody cetuximab in combination with radiation therapy in patients with advanced head and neck cancer. J Clin Oncol 19(13):3234–3243

    PubMed  CAS  Google Scholar 

  • Rocher-Ros V, Marco S, Mao JH, Gines S, Metzger D, Chambon P, Balmain A, Saura CA (2010) Presenilin modulates EGFR signaling and cell transformation by regulating the ubiquitin ligase Fbw7. Oncogene 29(20):2950–2961. doi:onc201057[pii]10.1038/onc.2010.57

    Article  PubMed  CAS  Google Scholar 

  • Smolen GA, Muir B, Mohapatra G, Barmettler A, Kim WJ, Rivera MN, Haserlat SM, Okimoto RA, Kwak E, Dahiya S, Garber JE, Bell DW, Sgroi DC, Chin L, Deng CX, Haber DA (2006) Frequent met oncogene amplification in a Brca1/Trp53 mouse model of mammary tumorigenesis. Cancer Res 66(7):3452–3455. doi:66/7/3452[pii]10.1158/0008-5472.CAN-05-4181

    Article  PubMed  CAS  Google Scholar 

  • Stommel JM, Kimmelman AC, Ying H, Nabioullin R, Ponugoti AH, Wiedemeyer R, Stegh AH, Bradner JE, Ligon KL, Brennan C, Chin L, DePinho RA (2007) Coactivation of receptor tyrosine kinases affects the response of tumor cells to targeted therapies. Science 318(5848):287–290. doi:1142946[pii]10.1126/science.1142946

    Article  PubMed  CAS  Google Scholar 

  • Wagner AD, Grothe W, Haerting J, Kleber G, Grothey A, Fleig WE (2006) Chemotherapy in advanced gastric cancer: a systematic review and meta-analysis based on aggregate data. J Clin Oncol 24(18):2903–2909. doi:24/18/2903[pii]10.1200/JCO.2005.05.0245

    Article  PubMed  CAS  Google Scholar 

  • Wild R, Fager K, Flefleh C, Kan D, Inigo I, Castaneda S, Luo FR, Camuso A, McGlinchey K, Rose WC (2006) Cetuximab preclinical antitumor activity (monotherapy and combination based) is not predicted by relative total or activated epidermal growth factor receptor tumor expression levels. Mol Cancer Ther 5(1):104–113. doi:5/1/104[pii]10.1158/1535-7163.MCT-05-0259

    Article  PubMed  CAS  Google Scholar 

  • Witta SE, Gemmill RM, Hirsch FR, Coldren CD, Hedman K, Ravdel L, Helfrich B, Dziadziuszko R, Chan DC, Sugita M, Chan Z, Baron A, Franklin W, Drabkin HA, Girard L, Gazdar AF, Minna JD, Bunn PA Jr (2006) Restoring E-cadherin expression increases sensitivity to epidermal growth factor receptor inhibitors in lung cancer cell lines. Cancer Res 66(2):944–950

    Article  PubMed  CAS  Google Scholar 

  • Witta SE, Dziadziuszko R, Yoshida K, Hedman K, Varella-Garcia M, Bunn PA Jr, Hirsch FR (2009) ErbB-3 expression is associated with E-cadherin and their coexpression restores response to gefitinib in non-small-cell lung cancer (NSCLC). Ann Oncol 20:689–695 Epub 2009 Jan 15

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by Deutsche Forschungsgemeinschaft (Sonderforschungsbereich 456, Teilprojekt A2) in collaboration with Teilprojekt B7.

Conflict of interest

We declare that there is no conflict of interest.

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Author notes

  1. Evelyn Eggenstein

    Present address: Lehrstuhl für Biologische Chemie, Technische Universität München, 85354, Freising-Weihenstephan, Germany

  2. Ingo Drexler

    Present address: Institut für Virologie, Heinrich-Heine-Universität, 40225, Düsseldorf, Germany

Authors and Affiliations

  1. Institut für Allgemeine Pathologie und Pathologische Anatomie, Technische Universität München, Klinikum rechts der Isar, Trogerstr. 18, 81675, Munich, Germany

    Stefan Heindl, Evelyn Eggenstein, Simone Keller, Julia Kneissl, Gisela Keller, Kathrin Mutze, Heinz Höfler & Birgit Luber

  2. Institut für Pathologie, Helmholtz Zentrum München, Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), 85764, Neuherberg, Germany

    Sandra Rauser & Heinz Höfler

  3. Institut für Virologie, Technische Universität München, Klinikum rechts der Isar, 81675, Munich, Germany

    Georg Gasteiger & Ingo Drexler

  4. Institut für Medizinische Statistik und Epidemiologie, Technische Universität München, Klinikum rechts der Isar, 81675, Munich, Germany

    Alexander Hapfelmeier

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  1. Stefan Heindl
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Correspondence to Birgit Luber.

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Stefan Heindl and Evelyn Eggenstein contributed equally to this work.

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Heindl, S., Eggenstein, E., Keller, S. et al. Relevance of MET activation and genetic alterations of KRAS and E-cadherin for cetuximab sensitivity of gastric cancer cell lines. J Cancer Res Clin Oncol 138, 843–858 (2012). https://doi.org/10.1007/s00432-011-1128-4

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