Acquired resistance to EGFR-targeted therapies incolorectal cancer

Molecular Oncology

Volumn 8, Issue 6, 2014, Pages 1084-1094

  Van Emburgh, Beth O ^a,b   Sartore Bianchi, Andrea ^c   Di Nicolantonio, Federica ^a,d   Siena, Salvatore ^c   Bardelli, Alberto ^a,d  

^a CANDIOLO CANCER INSTITUTE   (Italy)

^b FIRC INSTITUTE OF MOLECULAR ONCOLOGY   (Italy)

^c OSPEDALE NIGUARDA CA GRANDA   (Italy)

^d UNIVERSITY OF TURIN   (Italy)

Author keywords

Acquired resistance; Anti EGFR therapy; Cetuximab; Colorectal cancer; MET; Panitumumab; RAS

Indexed keywords

CETUXIMAB; DASATINIB; EPIDERMAL GROWTH FACTOR RECEPTOR; EPIDERMAL GROWTH FACTOR RECEPTOR 2; ERLOTINIB; GEFITINIB; K RAS PROTEIN; MITOGEN ACTIVATED PROTEIN KINASE; PANITUMUMAB; PROTEIN KINASE B; PROTEIN TYROSINE KINASE; RAF PROTEIN; RAS PROTEIN; SCATTER FACTOR RECEPTOR; VASCULOTROPIN RECEPTOR; ANTINEOPLASTIC AGENT;

CANCER PATIENT; CANCER RESISTANCE; CANCER THERAPY; CELL CLONE; CELL POPULATION; CHEMICAL ANALYSIS; COLORECTAL CANCER; COLORECTAL CANCER CELL LINE; CONVERGENT EVOLUTION; DRUG EFFICACY; ENZYME PHOSPHORYLATION; EPITHELIAL MESENCHYMAL TRANSITION; GENE MUTATION; GENETIC HETEROGENEITY; HUMAN; LONG TERM EXPOSURE; METASTATIC COLORECTAL CANCER; ONCOGENE SRC; REGULATORY MECHANISM; REVIEW; SIGNAL TRANSDUCTION; TUMOR XENOGRAFT; UBIQUITINATION; ANIMAL; ANTAGONISTS AND INHIBITORS; COLON; COLORECTAL NEOPLASMS; DRUG EFFECTS; DRUG RESISTANCE; METABOLISM; MOLECULARLY TARGETED THERAPY; PATHOLOGY; RECTUM;

ANIMALS; ANTINEOPLASTIC AGENTS; COLON; COLORECTAL NEOPLASMS; DRUG RESISTANCE, NEOPLASM; HUMANS; MAP KINASE SIGNALING SYSTEM; MOLECULAR TARGETED THERAPY; PROTO-ONCOGENE PROTEINS C-AKT; RAS PROTEINS; RECEPTOR, EPIDERMAL GROWTH FACTOR; RECTUM; SIGNAL TRANSDUCTION;

EID: 84914182003     PISSN: 15747891     EISSN: 18780261     Source Type: Journal    
DOI: 10.1016/j.molonc.2014.05.003     Document Type: Review

References (57)

1. Adam R., Wicherts D.A., de Haas R.J., Ciacio O., Lévi F., Paule B., Ducreux M., Azoulay D., Bismuth H., Castaing D. Patients with initially unresectable colorectal liver metastases: is there a possibility of cure?. J.Clin. Oncol. 2009, 27:1829-1835.
2. Amado R.G., Wolf M., Peeters M., Van Cutsem E., Siena S., Freeman D.J., Juan T., Sikorski R., Suggs S., Radinsky R., Patterson S.D., Chang D.D. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J.Clin. Oncol. 2008, 26:1626-1634.
3. Bardelli A., Corso S., Bertotti A., Hobor S., Valtorta E., Siravegna G., Sartore-Bianchi A., Scala E., Cassingena A., Zecchin D., Apicella M., Migliardi G., Galimi F., Lauricella C., Zanon C., Perera T., Veronese S., Corti G., Amatu A., Gambacorta M., Diaz L.A., Sausen M., Velculescu V.E., Comoglio P., Trusolino L., Di Nicolantonio F., Giordano S., Siena S. Amplification of the MET receptor drives resistance to anti-EGFR therapies in colorectal cancer. Cancer Discov. 2013, 3:658-673.
4. Benvenuti S., Sartore-Bianchi A., Di Nicolantonio F., Zanon C., Moroni M., Veronese S., Siena S., Bardelli A. 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. 2007, 67:2643-2648.
5. Bertotti A., Migliardi G., Galimi F., Sassi F., Torti D., Isella C., Corà D., Di Nicolantonio F., Buscarino M., Petti C., Ribero D., Russolillo N., Muratore A., Massucco P., Pisacane A., Molinaro L., Valtorta E., Sartore-Bianchi A., Risio M., Capussotti L., Gambacorta M., Siena S., Medico E., Sapino A., Marsoni S., Comoglio P.M., Bardelli A., Trusolino L. A molecularly annotated platform of patient-derived xenografts ("xenopatients") identifies HER2 as an effective therapeutic target in cetuximab-resistant colorectal cancer. Cancer Discov. 2011, 1:508-523.
6. Bettegowda C., Sausen M., Leary R.J., Kinde I., Wang Y., Agrawal N., Bartlett B.R., Wang H., Luber B., Alani R.M., Antonarakis E.S., Azad N.S., Bardelli A., Brem H., Cameron J.L., Lee C.C., Fecher L.A., Gallia G.L., Gibbs P., Le D., Giuntoli R.L., Goggins M., Hogarty M.D., Holdhoff M., Hong S.M., Jiao Y., Juhl H.H., Kim J.J., Siravegna G., Laheru D.A., Lauricella C., Lim M., Lipson E.J., Marie S.K., Netto G.J., Oliner K.S., Olivi A., Olsson L., Riggins G.J., Sartore-Bianchi A., Schmidt K., Shih l, Oba-Shinjo S.M., Siena S., Theodorescu D., Tie J., Harkins T.T., Veronese S., Wang T.L., Weingart J.D., Wolfgang C.L., Wood L.D., Xing D., Hruban R.H., Wu J., Allen P.J., Schmidt C.M., Choti M.A., Velculescu V.E., Kinzler K.W., Vogelstein B., Papadopoulos N., Diaz L.A. Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci. Transl Med. 2014, 6:224.
7. Bianco R., Rosa R., Damiano V., Daniele G., Gelardi T., Garofalo S., Tarallo V., De Falco S., Melisi D., Benelli R., Albini A., Ryan A., Ciardiello F., Tortora G. Vascular endothelial growth factor receptor-1 contributes to resistance to anti-epidermal growth factor receptor drugs in human cancer cells. Clin. Cancer Res. 2008, 14:5069-5080.
8. Brenner H., Kloor M., Pox C.P. Colorectal cancer. Lancet 2014, 383:1490-1502.
9. Ciardiello F., Bianco R., Caputo R., Damiano V., Troiani T., Melisi D., De Vita F., De Placido S., Bianco A.R., Tortora G. Antitumor activity of ZD6474, a vascular endothelial growth factor receptor tyrosine kinase inhibitor, in human cancer cells with acquired resistance to antiepidermal growth factor receptor therapy. Clin. Cancer Res. 2004, 10:784-793.
10. Cunningham D., Humblet Y., Siena S., Khayat D., Bleiberg H., Santoro A., Bets D., Mueser M., Harstrick A., Verslype C., Chau I., Van Cutsem E. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N.Engl. J. Med. 2004, 351:337-345.
11. De Roock W., Claes B., Bernasconi D., De Schutter J., Biesmans B., Fountzilas G., Kalogeras K.T., Kotoula V., Papamichael D., Laurent-Puig P., Penault-Llorca F., Rougier P., Vincenzi B., Santini D., Tonini G., Cappuzzo F., Frattini M., Molinari F., Saletti P., De Dosso S., Martini M., Bardelli A., Siena S., Sartore-Bianchi A., Tabernero J., Macarulla T., Di Fiore F., Gangloff A.O., Ciardiello F., Pfeiffer P., Qvortrup C., Hansen T.P., Van Cutsem E., Piessevaux H., Lambrechts D., Delorenzi M., Tejpar S. Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis. Lancet Oncol. 2010, 11:753-762.
12. Diaz L.A., Williams R.T., Wu J., Kinde I., Hecht J.R., Berlin J., Allen B., Bozic I., Reiter J.G., Nowak M.A., Kinzler K.W., Oliner K.S., Vogelstein B. The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers. Nature 2012, 486:537-540.
13. Douillard J.Y., Oliner K.S., Siena S., Tabernero J., Burkes R., Barugel M., Humblet Y., Bodoky G., Cunningham D., Jassem J., Rivera F., Kocákova I., Ruff P., Błasińska-Morawiec M., Šmakal M., Canon J.L., Rother M., Williams R., Rong A., Wiezorek J., Sidhu R., Patterson S.D. Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer. N.Engl. J. Med. 2013, 369:1023-1034.
14. Engelman J.A., Zejnullahu K., Mitsudomi T., Song Y., Hyland C., Park J.O., Lindeman N., Gale C.M., Zhao X., Christensen J., Kosaka T., Holmes A.J., Rogers A.M., Cappuzzo F., Mok T., Lee C., Johnson B.E., Cantley L.C., Jänne P.A. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science 2007, 316:1039-1043.
15. Esposito C., Rachiglio A.M., La Porta M.L., Sacco A., Roma C., Iannaccone A., Tatangelo F., Forgione L., Pasquale R., Barbaro A., Botti G., Ciardiello F., Normanno N. The S492R EGFR ectodomain mutation is never detected in KRAS wild type colorectal carcinoma before exposure to EGFR monoclonal antibodies. Cancer Biol. Ther. 2013, 14:1143-1146.
16. Flaherty K.T., Infante J.R., Daud A., Gonzalez R., Kefford R.F., Sosman J., Hamid O., Schuchter L., Cebon J., Ibrahim N., Kudchadkar R., Burris H.A., Falchook G., Algazi A., Lewis K., Long G.V., Puzanov I., Lebowitz P., Singh A., Little S., Sun P., Allred A., Ouellet D., Kim K.B., Patel K., Weber J. Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations. N.Engl. J. Med. 2012, 367:1694-1703.
17. Frattini M., Saletti P., Romagnani E., Martin V., Molinari F., Ghisletta M., Camponovo A., Etienne L.L., Cavalli F., Mazzucchelli L. PTEN loss of expression predicts cetuximab efficacy in metastatic colorectal cancer patients. Br. J. Cancer 2007, 97:1139-1145.
18. Gerlinger M., Rowan A.J., Horswell S., Larkin J., Endesfelder D., Gronroos E., Martinez P., Matthews N., Stewart A., Tarpey P., Varela I., Phillimore B., Begum S., McDonald N.Q., Butler A., Jones D., Raine K., Latimer C., Santos C.R., Nohadani M., Eklund A.C., Spencer-Dene B., Clark G., Pickering L., Stamp G., Gore M., Szallasi Z., Downward J., Futreal P.A., Swanton C. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N.Engl. J. Med. 2012, 366:883-892.
19. Hecht J.R., Mitchell E., Chidiac T., Scroggin C., Hagenstad C., Spigel D., Marshall J., Cohn A., McCollum D., Stella P., Deeter R., Shahin S., Amado R.G. A randomized phase IIIB trial of chemotherapy, bevacizumab, and panitumumab compared with chemotherapy and bevacizumab alone for metastatic colorectal cancer. J.Clin. Oncol. 2009, 27:672-680.
20. Jonker D.J., O'Callaghan C.J., Karapetis C.S., Zalcberg J.R., Tu D., Au H.J., Berry S.R., Krahn M., Price T., Simes R.J., Tebbutt N.C., van Hazel G., Wierzbicki R., Langer C., Moore M.J. Cetuximab for the treatment of colorectal cancer. N.Engl. J. Med. 2007, 357:2040-2048.
21. Karapetis C.S., Khambata-Ford S., Jonker D.J., O'Callaghan C.J., Tu D., Tebbutt N.C., Simes R.J., Chalchal H., Shapiro J.D., Robitaille S., Price T.J., Shepherd L., Au H.J., Langer C., Moore M.J., Zalcberg J.R. K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N.Engl. J. Med. 2008, 359:1757-1765.
22. Kobayashi S., Boggon T.J., Dayaram T., Janne P.A., Kocher O., Meyerson M., Johnson B.E., Eck M.J., Tenen D.G., Halmos B. EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N.Engl. J. Med. 2005, 352:786-792.
23. Laurent-Puig P., Cayre A., Manceau G., Buc E., Bachet J.B., Lecomte T., Rougier P., Lievre A., Landi B., Boige V., Ducreux M., Ychou M., Bibeau F., Bouché O., Reid J., Stone S., Penault-Llorca F. Analysis of PTEN, BRAF, and EGFR status in determining benefit from cetuximab therapy in wild-type KRAS metastatic colon cancer. J.Clin. Oncol. 2009, 27:5924-5930.
24. Li S., Schmitz K.R., Jeffrey P.D., Wiltzius J.J., Kussie P., Ferguson K.M. Structural basis for inhibition of the epidermal growth factor receptor by cetuximab. Cancer Cell 2005, 7:301-311.
25. Liska D., Chen C.T., Bachleitner-Hofmann T., Christensen J.G., Weiser M.R. HGF rescues colorectal cancer cells from EGFR inhibition via MET activation. Clin. Cancer Res. 2011, 17:472-482.
26. Lièvre A., Bachet J.B., Le Corre D., Boige V., Landi B., Emile J.F., Côté J.F., Tomasic G., Penna C., Ducreux M., Rougier P., Penault-Llorca F., Laurent-Puig P. KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer. Cancer Res. 2006, 66:3992-3995.
27. Lu Y., Li X., Liang K., Luwor R., Siddik Z.H., Mills G.B., Mendelsohn J., Fan Z. Epidermal growth factor receptor (EGFR) ubiquitination as a mechanism of acquired resistance escaping treatment by the anti-EGFR monoclonal antibody cetuximab. Cancer Res. 2007, 67:8240-8247.
28. Malvezzi M., Bertuccio P., Levi F., La Vecchia C., Negri E. European cancer mortality predictions for the year 2013. Ann. Oncol. 2013, 24:792-800.
29. Marsoni S., Bertotti A., Sartore-Bianchi A., Leone F., Lonardi S., Ciardiello F., Pinto C., Aglietta M., Zagonel V., Gambacorta M., Grigioni W.F., Rugge M., Risio M., Martino C., Valtorta E., Bardelli A., Trusolino L., Comoglio P.M., Siena S. Dual anti-HER2 treatment of patients with HER2-positive metastatic colorectal cancer: the HERACLES trial (HER2 Amplification for Colo-rectaL Cancer Enhanced Stratification). J.Clin. Oncol. 2013, 31.
30. Mendelsohn J., Baselga J. The EGF receptor family as targets for cancer therapy. Oncogene 2000, 19:6550-6565.
31. Misale S., Arena S., Lamba S., Siravegna G., Lallo A., Hobor S., Russo M., Buscarino M., Lazzari L., Sartore-Bianchi A., Bencardino K., Amatu A., Lauricella C., Valtorta E., Siena S., Di Nicolantonio F., Bardelli A. Blockade of EGFR and MEK intercepts heterogeneous mechanisms of acquired resistance to anti-EGFR therapies in colorectal cancer. Sci. Transl Med. 2014, 6:224-226.
32. Misale S., Yaeger R., Hobor S., Scala E., Janakiraman M., Liska D., Valtorta E., Schiavo R., Buscarino M., Siravegna G., Bencardino K., Cercek A., Chen C.T., Veronese S., Zanon C., Sartore-Bianchi A., Gambacorta M., Gallicchio M., Vakiani E., Boscaro V., Medico E., Weiser M., Siena S., Di Nicolantonio F., Solit D., Bardelli A. Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer. Nature 2012, 486:532-536.
33. Montagut C., Dalmases A., Bellosillo B., Crespo M., Pairet S., Iglesias M., Salido M., Gallen M., Marsters S., Tsai S.P., Minoche A., Seshagiri S., Somasekar S., Serrano S., Himmelbauer H., Bellmunt J., Rovira A., Settleman J., Bosch F., Albanell J. Identification of a mutation in the extracellular domain of the epidermal growth factor receptor conferring cetuximab resistance in colorectal cancer. Nat. Med. 2012, 18:221-223.
34. Moroni M., Veronese S., Benvenuti S., Marrapese G., Sartore-Bianchi A., Di Nicolantonio F., Gambacorta M., Siena S., Bardelli A. Gene copy number for epidermal growth factor receptor (EGFR) and clinical response to antiEGFR treatment in colorectal cancer: a cohort study. Lancet Oncol. 2005, 6:279-286.
35. Murtaza M., Dawson S.J., Tsui D.W., Gale D., Forshew T., Piskorz A.M., Parkinson C., Chin S.F., Kingsbury Z., Wong A.S., Marass F., Humphray S., Hadfield J., Bentley D., Chin T.M., Brenton J.D., Caldas C., Rosenfeld N. Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA. Nature 2013, 497:108-112.
36. Pao W., Miller V.A., Politi K.A., Riely G.J., Somwar R., Zakowski M.F., Kris M.G., Varmus H. Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. Plos Med. 2005, 2:e73.
37. Paranavitana C.M. Non-radioactive detection of K-ras mutations by nested allele specific PCR and oligonucleotide hybridization. Mol. Cell Probes 1998, 12:309-315.
38. Sartore-Bianchi A., Fieuws S., Veronese S., Moroni M., Personeni N., Frattini M., Torri V., Cappuzzo F., Vander Borght S., Martin V., Skokan M., Santoro A., Gambacorta M., Tejpar S., Varella-Garcia M., Siena S. Standardisation of EGFR FISH in colorectal cancer: results of an international interlaboratory reproducibility ring study. J.Clin. Pathol. 2012, 65:218-223.
39. Sartore-Bianchi A., Martini M., Molinari F., Veronese S., Nichelatti M., Artale S., Di Nicolantonio F., Saletti P., De Dosso S., Mazzucchelli L., Frattini M., Siena S., Bardelli A. PIK3CA mutations in colorectal cancer are associated with clinical resistance to EGFR-targeted monoclonal antibodies. Cancer Res. 2009, 69:1851-1857.
40. Sartore-Bianchi A., Moroni M., Veronese S., Carnaghi C., Bajetta E., Luppi G., Sobrero A., Barone C., Cascinu S., Colucci G., Cortesi E., Nichelatti M., Gambacorta M., Siena S. Epidermal growth factor receptor gene copy number and clinical outcome of metastatic colorectal cancer treated with panitumumab. J.Clin. Oncol. 2007, 25:3238-3245.
41. Scartozzi M., Mandolesi A., Giampieri R., Bittoni A., Pierantoni C., Zaniboni A., Galizia E., Giustini L., Silva R.R., Bisonni R., Berardi R., Biscotti T., Biagetti S., Bearzi I., Cascinu S. The role of HER-3 expression in the prediction of clinical outcome for advanced colorectal cancer patients receiving irinotecan and cetuximab. Oncologist 2011, 16:53-60.
42. Scartozzi M., Mandolesi A., Giampieri R., Pierantoni C., Loupakis F., Zaniboni A., Galizia E., Giustini L., Silva R.R., Bisonni R., Berardi R., Biagetti S., Menzo S., Falcone A., Bearzi I., Cascinu S. Insulin-like growth factor 1 expression correlates with clinical outcome in K-RAS wild type colorectal cancer patients treated with cetuximab and irinotecan. Int. J. Cancer 2010, 127:1941-1947.
43. Schmoll H.J., Van Cutsem E., Stein A., Valentini V., Glimelius B., Haustermans K., Nordlinger B., van de Velde C.J., Balmana J., Regula J., Nagtegaal I.D., Beets-Tan R.G., Arnold D., Ciardiello F., Hoff P., Kerr D., Köhne C.H., Labianca R., Price T., Scheithauer W., Sobrero A., Tabernero J., Aderka D., Barroso S., Bodoky G., Douillard J.Y., El Ghazaly H., Gallardo J., Garin A., Glynne-Jones R., Jordan K., Meshcheryakov A., Papamichail D., Pfeiffer P., Souglakos I., Turhal S., Cervantes A. ESMO consensus guidelines for management of patients with colon and rectal cancer. a personalized approach to clinical decision making. Ann. Oncol. 2012, 23:2479-2516.
44. Shien K., Toyooka S., Yamamoto H., Soh J., Jida M., Thu K.L., Hashida S., Maki Y., Ichihara E., Asano H., Tsukuda K., Takigawa N., Kiura K., Gazdar A.F., Lam W.L., Miyoshi S. Acquired resistance to EGFR inhibitors is associated with a manifestation of stem cell-like properties in cancer cells. Cancer Res. 2013, 73:3051-3061.
45. Siegel R., DeSantis C., Virgo K., Stein K., Mariotto A., Smith T., Cooper D., Gansler T., Lerro C., Fedewa S., Lin C., Leach C., Cannady R.S., Cho H., Scoppa S., Hachey M., Kirch R., Jemal A., Ward E. Cancer treatment and survivorship statistics, 2012. CA Cancer J. Clin. 2012, 62:220-241.
46. Siegel R., Naishadham D., Jemal A. Cancer statistics, 2013. CA Cancer J. Clin. 2013, 63:11-30.
47. Smith G., Bounds R., Wolf H., Steele R.J., Carey F.A., Wolf C.R. Activating K-Ras mutations outwith 'hotspot' codons in sporadic colorectal tumours - implications for personalised cancer medicine. Br. J. Cancer 2010, 102:693-703.
48. Sosman J.A., Kim K.B., Schuchter L., Gonzalez R., Pavlick A.C., Weber J.S., McArthur G.A., Hutson T.E., Moschos S.J., Flaherty K.T., Hersey P., Kefford R., Lawrence D., Puzanov I., Lewis K.D., Amaravadi R.K., Chmielowski B., Lawrence H.J., Shyr Y., Ye F., Li J., Nolop K.B., Lee R.J., Joe A.K., Ribas A. Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib. N.Engl. J. Med. 2012, 366:707-714.
49. Stintzing S., Jung A., Rossius L., Modest D.P., Fischer von Weikersthal L., Decker T., Mohler M., Scheithauer W., Kirchner T., Heinemann V. Analysis of KRAS/NRAS and BRAF mutations in FIRE-3: a randomized phase III study of FOLFIRI plus cetuximab or bevacizumab as first-line treatment for wild-type (WT) KRAS (exon 2) metastatic colorectal cancer (mCRC) patients. Eur. J. Cancer 2013, 49:LBA 17.
50. Takezawa K., Pirazzoli V., Arcila M.E., Nebhan C.A., Song X., de Stanchina E., Ohashi K., Janjigian Y.Y., Spitzler P.J., Melnick M.A., Riely G.J., Kris M.G., Miller V.A., Ladanyi M., Politi K., Pao W. HER2 amplification: a potential mechanism of acquired resistance to EGFR inhibition in EGFR-mutant lung cancers that lack the second-site EGFRT790M mutation. Cancer Discov. 2012, 2:922-933.
51. Tol J., Koopman M., Cats A., Rodenburg C.J., Creemers G.J., Schrama J.G., Erdkamp F.L., Vos A.H., van Groeningen C.J., Sinnige H.A., Richel D.J., Voest E.E., Dijkstra J.R., Vink-Borger M.E., Antonini N.F., Mol L., van Krieken J.H., Dalesio O., Punt C.J. Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer. N.Engl. J. Med. 2009, 360:563-572.
52. Troiani T., Martinelli E., Napolitano S., Vitagliano D., Ciuffreda L.P., Costantino S., Morgillo F., Capasso A., Sforza V., Nappi A., De Palma R., D'Aiuto E., Berrino L., Bianco R., Ciardiello F. Increased TGF-α as a mechanism of acquired resistance to the anti-EGFR inhibitor cetuximab through EGFR-MET interaction and activation of MET signaling in colon cancer cells. Clin. Cancer Res. 2013, 19:6751-6765.
53. Valtorta E., Misale S., Sartore-Bianchi A., Nagtegaal I.D., Paraf F., Lauricella C., Dimartino V., Hobor S., Jacobs B., Ercolani C., Lamba S., Scala E., Veronese S., Laurent-Puig P., Siena S., Tejpar S., Mottolese M., Punt C.J., Gambacorta M., Bardelli A., Di Nicolantonio F. KRAS gene amplification in colorectal cancer and impact on response to EGFR-targeted therapy. Int. J. Cancer 2013, 133:1259-1265.
54. Van Cutsem E., Kohne C.H., Hitre E., Zaluski J., Chang Chien C.R., Makhson A., D'Haens G., Pinter T., Lim R., Bodoky G., Roh J.K., Folprecht G., Ruff P., Stroh C., Tejpar S., Schlichting M., Nippgen J., Rougier P. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N.Engl. J. Med. 2009, 360:1408-1417.
55. Van Cutsem E., Peeters M., Siena S., Humblet Y., Hendlisz A., Neyns B., Canon J.L., Van Laethem J.L., Maurel J., Richardson G., Wolf M., Amado R.G. Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J.Clin. Oncol. 2007, 25:1658-1664.
56. Wheeler D.L., Iida M., Kruser T.J., Nechrebecki M.M., Dunn E.F., Armstrong E.A., Huang S., Harari P.M. Epidermal growth factor receptor cooperates with Src family kinases in acquired resistance to cetuximab. Cancer Biol. Ther. 2009, 8:696-703.
57. Yonesaka K., Zejnullahu K., Okamoto I., Satoh T., Cappuzzo F., Souglakos J., Ercan D., Rogers A., Roncalli M., Takeda M., Fujisaka Y., Philips J., Shimizu T., Maenishi O., Cho Y., Sun J., Destro A., Taira K., Takeda K., Okabe T., Swanson J., Itoh H., Takada M., Lifshits E., Okuno K., Engelman J.A., Shivdasani R.A., Nishio K., Fukuoka M., Varella-Garcia M., Nakagawa K., Jänne P.A. Activation of ERBB2 signaling causes resistance to the EGFR-directed therapeutic antibody cetuximab. Sci. Transl Med. 2011, 3:99-186.