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Published in: Journal of Cancer Research and Clinical Oncology 2/2013

01-02-2013 | Original Paper

KRAS p.G13D mutations are associated with sensitivity to anti-EGFR antibody treatment in colorectal cancer cell lines

Authors: Isabelle Messner, Giuseppe Cadeddu, Wolfgang Huckenbeck, Helen J. Knowles, Helmut E. Gabbert, Stephan E. Baldus, Karl-Ludwig Schaefer

Published in: Journal of Cancer Research and Clinical Oncology | Issue 2/2013

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Abstract

Purpose

Targeted therapies using the anti-EGFR antibodies panitumumab (Pmab) or cetuximab (Cmab) are currently restricted to patients with metastatic colorectal adenocarcinoma whose tumours do not show a mutation in KRAS. However, recent retrospective studies indicated that patients with tumours mutated in codon 13 of KRAS may benefit from treatment with Cmab in contrast to patients with tumours mutated in KRAS codon 12.

Methods

To study the functional impact of the subtype of KRAS mutations on the efficiency of EGFR-targeted therapies, we correlated the KRAS mutation status of 15 colorectal carcinoma cell lines with the in vitro sensitivity of these cells to Cmab/Pmab. Mutations in the potential predictive biomarkers BRAF and PIK3CA as well as protein expression of EGFR and PTEN were also determined.

Results

Four out of seven KRAS-mutated cell lines were characterised by the p.G13D mutation. Treatment of these cells using Cmab/Pmab induced a significant growth inhibition in contrast to cell lines showing a KRAS mutation at codon 12 or 61. Out of the eight KRAS wild-type cell lines, five were insensitive to Cmab/Pmab. These cell lines were characterised either by BRAF mutation or by absence of EGFR or PTEN protein expression.

Conclusions

Since KRAS p.G13D-mutated tumour cells may respond to EGFR-targeted therapy, we suggest including subtype analysis of KRAS mutations in prospective clinical trials. In KRAS wild-type tumour cells, BRAF mutations and loss of EGFR or PTEN expression may lead to resistance to EGFR-targeted therapy and should be considered as additional negative predictive biomarkers.
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Literature
go back to reference Alldinger I, Schaefer KL, Goedde D, Ottaviano L, Dirksen U, Ranft A, Juergens H, Gabbert HE, Knoefel WT, Poremba C (2007) Microsatellite instability in Ewing tumor is not associated with loss of mismatch repair protein expression. J Cancer Res Clin Oncol 133(10):749–759PubMedCrossRef Alldinger I, Schaefer KL, Goedde D, Ottaviano L, Dirksen U, Ranft A, Juergens H, Gabbert HE, Knoefel WT, Poremba C (2007) Microsatellite instability in Ewing tumor is not associated with loss of mismatch repair protein expression. J Cancer Res Clin Oncol 133(10):749–759PubMedCrossRef
go back to reference Amado RG, Wolf M, Peeters M, Van Cutsem E, Siena S, Freeman DJ, Juan T, Sikorski R, Suggs S, Radinsky R, Patterson SD, Chang DD (2008) Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol 26(10):1626–1634PubMedCrossRef Amado RG, Wolf M, Peeters M, Van Cutsem E, Siena S, Freeman DJ, Juan T, Sikorski R, Suggs S, Radinsky R, Patterson SD, Chang DD (2008) Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol 26(10):1626–1634PubMedCrossRef
go back to reference Andreyev HJ, Norman AR, Cunningham D, Oates J, Dix BR, Iacopetta BJ, Young J, Walsh T, Ward R, Hawkins N, Beranek M, Jandik P, Benamouzig R, Jullian E, Laurent-Puig P, Olschwang S, Muller O, Hoffmann I, Rabes HM, Zietz C, Troungos C, Valavanis C, Yuen ST, Ho JW, Croke CT, O’Donoghue DP, Giaretti W, Rapallo A, Russo A, Bazan V, Tanaka M, Omura K, Azuma T, Ohkusa T, Fujimori T, Ono Y, Pauly M, Faber C, Glaesener R, de Goeij AF, Arends JW, Andersen SN, Lovig T, Breivik J, Gaudernack G, Clausen OP, De Angelis PD, Meling GI, Rognum TO, Smith R, Goh HS, Font A, Rosell R, Sun XF, Zhang H, Benhattar J, Losi L, Lee JQ, Wang ST, Clarke PA, Bell S, Quirke P, Bubb VJ, Piris J, Cruickshank NR, Morton D, Fox JC, Al-Mulla F, Lees N, Hall CN, Snary D, Wilkinson K, Dillon D, Costa J, Pricolo VE, Finkelstein SD, Thebo JS, Senagore AJ, Halter SA, Wadler S, Malik S, Krtolica K, Urosevic N (2001) Kirsten ras mutations in patients with colorectal cancer: the ‘RASCAL II’ study. Br J Cancer 85(5):692–696PubMedCrossRef Andreyev HJ, Norman AR, Cunningham D, Oates J, Dix BR, Iacopetta BJ, Young J, Walsh T, Ward R, Hawkins N, Beranek M, Jandik P, Benamouzig R, Jullian E, Laurent-Puig P, Olschwang S, Muller O, Hoffmann I, Rabes HM, Zietz C, Troungos C, Valavanis C, Yuen ST, Ho JW, Croke CT, O’Donoghue DP, Giaretti W, Rapallo A, Russo A, Bazan V, Tanaka M, Omura K, Azuma T, Ohkusa T, Fujimori T, Ono Y, Pauly M, Faber C, Glaesener R, de Goeij AF, Arends JW, Andersen SN, Lovig T, Breivik J, Gaudernack G, Clausen OP, De Angelis PD, Meling GI, Rognum TO, Smith R, Goh HS, Font A, Rosell R, Sun XF, Zhang H, Benhattar J, Losi L, Lee JQ, Wang ST, Clarke PA, Bell S, Quirke P, Bubb VJ, Piris J, Cruickshank NR, Morton D, Fox JC, Al-Mulla F, Lees N, Hall CN, Snary D, Wilkinson K, Dillon D, Costa J, Pricolo VE, Finkelstein SD, Thebo JS, Senagore AJ, Halter SA, Wadler S, Malik S, Krtolica K, Urosevic N (2001) Kirsten ras mutations in patients with colorectal cancer: the ‘RASCAL II’ study. Br J Cancer 85(5):692–696PubMedCrossRef
go back to reference Atkins D, Reiffen KA, Tegtmeier CL, Winther H, Bonato MS, Storkel S (2004) Immunohistochemical detection of EGFR in paraffin-embedded tumor tissues: variation in staining intensity due to choice of fixative and storage time of tissue sections. J Histochem Cytochem 52(7):893–901PubMedCrossRef Atkins D, Reiffen KA, Tegtmeier CL, Winther H, Bonato MS, Storkel S (2004) Immunohistochemical detection of EGFR in paraffin-embedded tumor tissues: variation in staining intensity due to choice of fixative and storage time of tissue sections. J Histochem Cytochem 52(7):893–901PubMedCrossRef
go back to reference Baldus SE, Schaefer KL, Engers R, Hartleb D, Stoecklein NH, Gabbert HE (2010) Prevalence and heterogeneity of KRAS, BRAF, and PIK3CA mutations in primary colorectal adenocarcinomas and their corresponding metastases. Clin Cancer Res 16(3):790–799PubMedCrossRef Baldus SE, Schaefer KL, Engers R, Hartleb D, Stoecklein NH, Gabbert HE (2010) Prevalence and heterogeneity of KRAS, BRAF, and PIK3CA mutations in primary colorectal adenocarcinomas and their corresponding metastases. Clin Cancer Res 16(3):790–799PubMedCrossRef
go back to reference Bardelli A, Siena S (2010) Molecular mechanisms of resistance to cetuximab and panitumumab in colorectal cancer. J Clin Oncol 28(7):1254–1261PubMedCrossRef Bardelli A, Siena S (2010) Molecular mechanisms of resistance to cetuximab and panitumumab in colorectal cancer. J Clin Oncol 28(7):1254–1261PubMedCrossRef
go back to reference Benvenuti S, Sartore-Bianchi A, Di Nicolantonio F, Zanon C, Moroni M, Veronese S, Siena S, Bardelli A (2007) Oncogenic activation of the RAS/RAF signaling pathway impairs the response of metastatic colorectal cancers to anti-epidermal growth factor receptor antibody therapies. Cancer Res 67(6):2643–2648PubMedCrossRef Benvenuti S, Sartore-Bianchi A, Di Nicolantonio F, Zanon C, Moroni M, Veronese S, Siena S, Bardelli A (2007) Oncogenic activation of the RAS/RAF signaling pathway impairs the response of metastatic colorectal cancers to anti-epidermal growth factor receptor antibody therapies. Cancer Res 67(6):2643–2648PubMedCrossRef
go back to reference Bibeau F, Boissiere-Michot F, Sabourin JC, Gourgou-Bourgade S, Radal M, Penault-Llorca F, Rochaix P, Arnould L, Bralet MP, Azria D, Ychou M (2006) Assessment of epidermal growth factor receptor (EGFR) expression in primary colorectal carcinomas and their related metastases on tissue sections and tissue microarray. Virchows Arch 449(3):281–287PubMedCrossRef Bibeau F, Boissiere-Michot F, Sabourin JC, Gourgou-Bourgade S, Radal M, Penault-Llorca F, Rochaix P, Arnould L, Bralet MP, Azria D, Ychou M (2006) Assessment of epidermal growth factor receptor (EGFR) expression in primary colorectal carcinomas and their related metastases on tissue sections and tissue microarray. Virchows Arch 449(3):281–287PubMedCrossRef
go back to reference 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):1803–1810PubMedCrossRef 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):1803–1810PubMedCrossRef
go back to reference De Roock W, Jonker DJ, Di Nicolantonio F, Sartore-Bianchi A, Tu D, Siena S, Lamba S, Arena S, Frattini M, Piessevaux H, Van Cutsem E, O’Callaghan CJ, Khambata-Ford S, Zalcberg JR, Simes J, Karapetis CS, Bardelli A, Tejpar S (2010) Association of KRAS p.G13D mutation with outcome in patients with chemotherapy-refractory metastatic colorectal cancer treated with cetuximab. JAMA 304(16):1812–1820PubMedCrossRef De Roock W, Jonker DJ, Di Nicolantonio F, Sartore-Bianchi A, Tu D, Siena S, Lamba S, Arena S, Frattini M, Piessevaux H, Van Cutsem E, O’Callaghan CJ, Khambata-Ford S, Zalcberg JR, Simes J, Karapetis CS, Bardelli A, Tejpar S (2010) Association of KRAS p.G13D mutation with outcome in patients with chemotherapy-refractory metastatic colorectal cancer treated with cetuximab. JAMA 304(16):1812–1820PubMedCrossRef
go back to reference Di Fiore F, Blanchard F, Charbonnier F, Le Pessot F, Lamy A, Galais MP, Bastit L, Killian A, Sesboue R, Tuech JJ, Queuniet AM, Paillot B, Sabourin JC, Michot F, Michel P, Frebourg T (2007) Clinical relevance of KRAS mutation detection in metastatic colorectal cancer treated by Cetuximab plus chemotherapy. Br J Cancer 96(8):1166–1169. doi:10.1038/sj.bjc.6603685 PubMedCrossRef Di Fiore F, Blanchard F, Charbonnier F, Le Pessot F, Lamy A, Galais MP, Bastit L, Killian A, Sesboue R, Tuech JJ, Queuniet AM, Paillot B, Sabourin JC, Michot F, Michel P, Frebourg T (2007) Clinical relevance of KRAS mutation detection in metastatic colorectal cancer treated by Cetuximab plus chemotherapy. Br J Cancer 96(8):1166–1169. doi:10.​1038/​sj.​bjc.​6603685 PubMedCrossRef
go back to reference Edkins S, O’Meara S, Parker A, Stevens C, Reis M, Jones S, Greenman C, Davies H, Dalgliesh G, Forbes S, Hunter C, Smith R, Stephens P, Goldstraw P, Nicholson A, Chan TL, Velculescu VE, Yuen ST, Leung SY, Stratton MR, Futreal PA (2006) Recurrent KRAS codon 146 mutations in human colorectal cancer. Cancer Biol Ther 5(8):928–932PubMedCrossRef Edkins S, O’Meara S, Parker A, Stevens C, Reis M, Jones S, Greenman C, Davies H, Dalgliesh G, Forbes S, Hunter C, Smith R, Stephens P, Goldstraw P, Nicholson A, Chan TL, Velculescu VE, Yuen ST, Leung SY, Stratton MR, Futreal PA (2006) Recurrent KRAS codon 146 mutations in human colorectal cancer. Cancer Biol Ther 5(8):928–932PubMedCrossRef
go back to reference Finkelstein SD, Sayegh R, Bakker A, Swalsky P (1993) Determination of tumor aggressiveness in colorectal cancer by K-ras-2 analysis. Arch Surg 128(5):526–531 discussion 531–522PubMedCrossRef Finkelstein SD, Sayegh R, Bakker A, Swalsky P (1993) Determination of tumor aggressiveness in colorectal cancer by K-ras-2 analysis. Arch Surg 128(5):526–531 discussion 531–522PubMedCrossRef
go back to reference Guerrero S, Casanova I, Farre L, Mazo A, Capella G, Mangues R (2000) K-ras codon 12 mutation induces higher level of resistance to apoptosis and predisposition to anchorage-independent growth than codon 13 mutation or proto-oncogene overexpression. Cancer Res 60(23):6750–6756PubMed Guerrero S, Casanova I, Farre L, Mazo A, Capella G, Mangues R (2000) K-ras codon 12 mutation induces higher level of resistance to apoptosis and predisposition to anchorage-independent growth than codon 13 mutation or proto-oncogene overexpression. Cancer Res 60(23):6750–6756PubMed
go back to reference Ikenoue T, Hikiba Y, Kanai F, Tanaka Y, Imamura J, Imamura T, Ohta M, Ijichi H, Tateishi K, Kawakami T, Aragaki J, Matsumura M, Kawabe T, Omata M (2003) Functional analysis of mutations within the kinase activation segment of B-Raf in human colorectal tumors. Cancer Res 63(23):8132–8137PubMed Ikenoue T, Hikiba Y, Kanai F, Tanaka Y, Imamura J, Imamura T, Ohta M, Ijichi H, Tateishi K, Kawakami T, Aragaki J, Matsumura M, Kawabe T, Omata M (2003) Functional analysis of mutations within the kinase activation segment of B-Raf in human colorectal tumors. Cancer Res 63(23):8132–8137PubMed
go back to reference Italiano A, Saint-Paul MC, Caroli-Bosc FX, Francois E, Bourgeon A, Benchimol D, Gugenheim J, Michiels JF (2005) Epidermal growth factor receptor (EGFR) status in primary colorectal tumors correlates with EGFR expression in related metastatic sites: biological and clinical implications. Ann Oncol 16(9):1503–1507PubMedCrossRef Italiano A, Saint-Paul MC, Caroli-Bosc FX, Francois E, Bourgeon A, Benchimol D, Gugenheim J, Michiels JF (2005) Epidermal growth factor receptor (EGFR) status in primary colorectal tumors correlates with EGFR expression in related metastatic sites: biological and clinical implications. Ann Oncol 16(9):1503–1507PubMedCrossRef
go back to reference Jancik S, Drabek J, Radzioch D, Hajduch M (2010) Clinical relevance of KRAS in human cancers. J Biomed Biotechnol 2010:150960PubMed Jancik S, Drabek J, Radzioch D, Hajduch M (2010) Clinical relevance of KRAS in human cancers. J Biomed Biotechnol 2010:150960PubMed
go back to reference Jhawer M, Goel S, Wilson AJ, Montagna C, Ling YH, Byun DS, Nasser S, Arango D, Shin J, Klampfer L, Augenlicht LH, Perez-Soler R, 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):1953–1961PubMedCrossRef Jhawer M, Goel S, Wilson AJ, Montagna C, Ling YH, Byun DS, Nasser S, Arango D, Shin J, Klampfer L, Augenlicht LH, Perez-Soler R, 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):1953–1961PubMedCrossRef
go back to reference Khambata-Ford S, Garrett CR, Meropol NJ, Basik M, Harbison CT, Wu S, Wong TW, Huang X, Takimoto CH, Godwin AK, Tan BR, Krishnamurthi SS, Burris HA 3rd, Poplin EA, Hidalgo M, Baselga J, Clark EA, Mauro DJ (2007) Expression of epiregulin and amphiregulin and K-ras mutation status predict disease control in metastatic colorectal cancer patients treated with cetuximab. J Clin Oncol 25(22):3230–3237PubMedCrossRef Khambata-Ford S, Garrett CR, Meropol NJ, Basik M, Harbison CT, Wu S, Wong TW, Huang X, Takimoto CH, Godwin AK, Tan BR, Krishnamurthi SS, Burris HA 3rd, Poplin EA, Hidalgo M, Baselga J, Clark EA, Mauro DJ (2007) Expression of epiregulin and amphiregulin and K-ras mutation status predict disease control in metastatic colorectal cancer patients treated with cetuximab. J Clin Oncol 25(22):3230–3237PubMedCrossRef
go back to reference Lenz HJ, Van Cutsem E, Khambata-Ford S, Mayer RJ, Gold P, Stella P, Mirtsching B, Cohn AL, Pippas AW, Azarnia N, Tsuchihashi Z, Mauro DJ, Rowinsky EK (2006) Multicenter phase II and translational study of cetuximab in metastatic colorectal carcinoma refractory to irinotecan, oxaliplatin, and fluoropyrimidines. J Clin Oncol 24(30):4914–4921PubMedCrossRef Lenz HJ, Van Cutsem E, Khambata-Ford S, Mayer RJ, Gold P, Stella P, Mirtsching B, Cohn AL, Pippas AW, Azarnia N, Tsuchihashi Z, Mauro DJ, Rowinsky EK (2006) Multicenter phase II and translational study of cetuximab in metastatic colorectal carcinoma refractory to irinotecan, oxaliplatin, and fluoropyrimidines. J Clin Oncol 24(30):4914–4921PubMedCrossRef
go back to reference Lievre A, Bachet JB, Boige V, Cayre A, Le Corre D, Buc E, Ychou M, Bouche O, Landi B, Louvet C, Andre T, Bibeau F, Diebold MD, Rougier P, Ducreux M, Tomasic G, Emile JF, Penault-Llorca F, Laurent-Puig P (2008) KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab. J Clin Oncol 26(3):374–379PubMedCrossRef Lievre A, Bachet JB, Boige V, Cayre A, Le Corre D, Buc E, Ychou M, Bouche O, Landi B, Louvet C, Andre T, Bibeau F, Diebold MD, Rougier P, Ducreux M, Tomasic G, Emile JF, Penault-Llorca F, Laurent-Puig P (2008) KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab. J Clin Oncol 26(3):374–379PubMedCrossRef
go back to reference Linardou H, Dahabreh IJ, Kanaloupiti D, Siannis F, Bafaloukos D, Kosmidis P, Papadimitriou CA, Murray S (2008) Assessment of somatic k-RAS mutations as a mechanism associated with resistance to EGFR-targeted agents: a systematic review and meta-analysis of studies in advanced non-small-cell lung cancer and metastatic colorectal cancer. Lancet Oncol 9(10):962–972PubMedCrossRef Linardou H, Dahabreh IJ, Kanaloupiti D, Siannis F, Bafaloukos D, Kosmidis P, Papadimitriou CA, Murray S (2008) Assessment of somatic k-RAS mutations as a mechanism associated with resistance to EGFR-targeted agents: a systematic review and meta-analysis of studies in advanced non-small-cell lung cancer and metastatic colorectal cancer. Lancet Oncol 9(10):962–972PubMedCrossRef
go back to reference Lopez-Albaitero A, Ferris RL (2007) Immune activation by epidermal growth factor receptor specific monoclonal antibody therapy for head and neck cancer. Arch Otollanyngol Head Neck Surg 133:1277–1281CrossRef Lopez-Albaitero A, Ferris RL (2007) Immune activation by epidermal growth factor receptor specific monoclonal antibody therapy for head and neck cancer. Arch Otollanyngol Head Neck Surg 133:1277–1281CrossRef
go back to reference Loupakis F, Ruzzo A, Cremolini C, Vincenzi B, Salvatore L, Santini D, Masi G, Stasi I, Canestrari E, Rulli E, Floriani I, Bencardino K, Galluccio N, Catalano V, Tonini G, Magnani M, Fontanini G, Basolo F, Falcone A, Graziano F (2009) KRAS codon 61, 146 and BRAF mutations predict resistance to cetuximab plus irinotecan in KRAS codon 12 and 13 wild-type metastatic colorectal cancer. Br J Cancer 101(4):715–721PubMedCrossRef Loupakis F, Ruzzo A, Cremolini C, Vincenzi B, Salvatore L, Santini D, Masi G, Stasi I, Canestrari E, Rulli E, Floriani I, Bencardino K, Galluccio N, Catalano V, Tonini G, Magnani M, Fontanini G, Basolo F, Falcone A, Graziano F (2009) KRAS codon 61, 146 and BRAF mutations predict resistance to cetuximab plus irinotecan in KRAS codon 12 and 13 wild-type metastatic colorectal cancer. Br J Cancer 101(4):715–721PubMedCrossRef
go back to reference Normanno N, Tejpar S, Morgillo F, De Luca A, Van Cutsem E, Ciardiello F (2009) Implications for KRAS status and EGFR-targeted therapies in metastatic CRC. Nat Rev Clin Oncol 6(9):519–527PubMedCrossRef Normanno N, Tejpar S, Morgillo F, De Luca A, Van Cutsem E, Ciardiello F (2009) Implications for KRAS status and EGFR-targeted therapies in metastatic CRC. Nat Rev Clin Oncol 6(9):519–527PubMedCrossRef
go back to reference Ottaviano L, Schaefer KL, Gajewski M, Huckenbeck W, Baldus S, Rogel U, Mackintosh C, de Alava E, Myklebost O, Kresse SH, Meza-Zepeda LA, Serra M, Cleton-Jansen AM, Hogendoorn PC, Buerger H, Aigner T, Gabbert HE, Poremba C (2010) Molecular characterization of commonly used cell lines for bone tumor research: a trans-European EuroBoNet effort. Genes Chromosom Cancer 49(1):40–51PubMedCrossRef Ottaviano L, Schaefer KL, Gajewski M, Huckenbeck W, Baldus S, Rogel U, Mackintosh C, de Alava E, Myklebost O, Kresse SH, Meza-Zepeda LA, Serra M, Cleton-Jansen AM, Hogendoorn PC, Buerger H, Aigner T, Gabbert HE, Poremba C (2010) Molecular characterization of commonly used cell lines for bone tumor research: a trans-European EuroBoNet effort. Genes Chromosom Cancer 49(1):40–51PubMedCrossRef
go back to reference Paez JG, Janne PA, Lee JC, Tracy S, Greulich H, Gabriel S, Herman P, Kaye FJ, Lindeman N, Boggon TJ, Naoki K, Sasaki H, Fujii Y, Eck MJ, Sellers WR, Johnson BE, Meyerson M (2004) EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 304(5676):1497–1500PubMedCrossRef Paez JG, Janne PA, Lee JC, Tracy S, Greulich H, Gabriel S, Herman P, Kaye FJ, Lindeman N, Boggon TJ, Naoki K, Sasaki H, Fujii Y, Eck MJ, Sellers WR, Johnson BE, Meyerson M (2004) EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 304(5676):1497–1500PubMedCrossRef
go back to reference Peeters M, Douillard JY, Van Cutsem E, Siena S, Zhang K, Williams RT et al. (2012) Mutant (MT) KRAS codon 12 and 13 alleles in patients (pts) with metastatic colorectal cancer (mCRC): assessment as prognostic and predictive biomarkers of response to panitumumab (pmab). J Clin Oncol 30(suppl); abstr 383 Peeters M, Douillard JY, Van Cutsem E, Siena S, Zhang K, Williams RT et al. (2012) Mutant (MT) KRAS codon 12 and 13 alleles in patients (pts) with metastatic colorectal cancer (mCRC): assessment as prognostic and predictive biomarkers of response to panitumumab (pmab). J Clin Oncol 30(suppl); abstr 383
go back to reference Schaefer KL, Brachwitz K, Braun Y, Diallo R, Wai DH, Zahn S, Schneider DT, Kuhnen C, Vollmann A, Brockhoff G, Gabbert HE, Poremba C (2006) Constitutive activation of neuregulin/ERBB3 signaling pathway in clear cell sarcoma of soft tissue. Neoplasia 8(7):613–622PubMedCrossRef Schaefer KL, Brachwitz K, Braun Y, Diallo R, Wai DH, Zahn S, Schneider DT, Kuhnen C, Vollmann A, Brockhoff G, Gabbert HE, Poremba C (2006) Constitutive activation of neuregulin/ERBB3 signaling pathway in clear cell sarcoma of soft tissue. Neoplasia 8(7):613–622PubMedCrossRef
go back to reference Siena S, Sartore-Bianchi A, Di Nicolantonio F, Balfour J, Bardelli A (2009) Biomarkers predicting clinical outcome of epidermal growth factor receptor-targeted therapy in metastatic colorectal cancer. J Natl Cancer Inst 101(19):1308–1324PubMedCrossRef Siena S, Sartore-Bianchi A, Di Nicolantonio F, Balfour J, Bardelli A (2009) Biomarkers predicting clinical outcome of epidermal growth factor receptor-targeted therapy in metastatic colorectal cancer. J Natl Cancer Inst 101(19):1308–1324PubMedCrossRef
go back to reference Silvestris N, Tommasi S, Petriella D, Santini D, Fistola E, Russo A, Numico G, Tonini G, Maiello E, Colucci G (2009) The dark side of the moon: the PI3K/PTEN/AKT pathway in colorectal carcinoma. Oncology 77(Suppl 1):69–74PubMedCrossRef Silvestris N, Tommasi S, Petriella D, Santini D, Fistola E, Russo A, Numico G, Tonini G, Maiello E, Colucci G (2009) The dark side of the moon: the PI3K/PTEN/AKT pathway in colorectal carcinoma. Oncology 77(Suppl 1):69–74PubMedCrossRef
go back to reference Tejpar S, Bertagnolli M, Bosman F, Lenz HJ, Garraway L, Waldman F, Warren R, Bild A, Collins-Brennan D, Hahn H, Harkin DP, Kennedy R, Ilyas M, Morreau H, Proutski V, Swanton C, Tomlinson I, Delorenzi M, Fiocca R, Van Cutsem E, Roth A (2010) Prognostic and predictive biomarkers in resected colon cancer: current status and future perspectives for integrating genomics into biomarker discovery. Oncologist 15(4):390–404PubMedCrossRef Tejpar S, Bertagnolli M, Bosman F, Lenz HJ, Garraway L, Waldman F, Warren R, Bild A, Collins-Brennan D, Hahn H, Harkin DP, Kennedy R, Ilyas M, Morreau H, Proutski V, Swanton C, Tomlinson I, Delorenzi M, Fiocca R, Van Cutsem E, Roth A (2010) Prognostic and predictive biomarkers in resected colon cancer: current status and future perspectives for integrating genomics into biomarker discovery. Oncologist 15(4):390–404PubMedCrossRef
go back to reference Tejpar S, Celik I, Schlichting M, Sartorius U, Bokemeyer C, Van Cutsem E (2012) Association of KRAS G13D tumor mutations with outcome in patients with metastatic colorectal cancer treated with first-line chemotherapy with or without cetuximab. J Clin Oncol. doi:10.1200/JCO.2012.42.2592 Tejpar S, Celik I, Schlichting M, Sartorius U, Bokemeyer C, Van Cutsem E (2012) Association of KRAS G13D tumor mutations with outcome in patients with metastatic colorectal cancer treated with first-line chemotherapy with or without cetuximab. J Clin Oncol. doi:10.​1200/​JCO.​2012.​42.​2592
go back to reference Tol J, Dijkstra JR, Klomp M, Teerenstra S, Dommerholt M, Vink-Borger ME, van Cleef PH, van Krieken JH, Punt CJ, Nagtegaal ID (2010) Markers for EGFR pathway activation as predictor of outcome in metastatic colorectal cancer patients treated with or without cetuximab. Eur J Cancer 46(11):1997–2009PubMedCrossRef Tol J, Dijkstra JR, Klomp M, Teerenstra S, Dommerholt M, Vink-Borger ME, van Cleef PH, van Krieken JH, Punt CJ, Nagtegaal ID (2010) Markers for EGFR pathway activation as predictor of outcome in metastatic colorectal cancer patients treated with or without cetuximab. Eur J Cancer 46(11):1997–2009PubMedCrossRef
go back to reference Yang XD, Jia XC, Corvalan JR, Wang P, Davis CG (2001) Development of ABX-EGF, a fully human anti-EGF receptor monoclonal antibody, for cancer therapy. Crit Rev Oncol Hematol 38(1):17–23PubMedCrossRef Yang XD, Jia XC, Corvalan JR, Wang P, Davis CG (2001) Development of ABX-EGF, a fully human anti-EGF receptor monoclonal antibody, for cancer therapy. Crit Rev Oncol Hematol 38(1):17–23PubMedCrossRef
Metadata
Title
KRAS p.G13D mutations are associated with sensitivity to anti-EGFR antibody treatment in colorectal cancer cell lines
Authors
Isabelle Messner
Giuseppe Cadeddu
Wolfgang Huckenbeck
Helen J. Knowles
Helmut E. Gabbert
Stephan E. Baldus
Karl-Ludwig Schaefer
Publication date
01-02-2013
Publisher
Springer-Verlag
Published in
Journal of Cancer Research and Clinical Oncology / Issue 2/2013
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-012-1319-7

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Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.