• Benvenuti, S., Sartore-Bianchi, A., Di Nicolantonio, F., Zanon, C., Moroni, M., Veronese, S., et al. (2007) Activation of pp60c-src protein kinase activity in human colon carcinoma. Proc. Natl Acad. Sci. USA , 84, 2251-2255. • Bonner, J., Ezekiel, M., Robert, F., Meredith, R., Spencer, S., & Waksal, H. (2000. Phase I Study of Anti-Epidermal Growth Factor Receptor Antibody Cetuximab in Combination With Radiation Therapy in Patients With Advanced Head and Neck Cancer. Proc. Annu. Meet. Am. Soc. Clin. Oncol. ,19 (4a).• Borner, M., Koeberle, D., Von Moos, R., Saletti, P., Rauch, D., Hess, V., et al. (2008). Adding cetuximab to capecitabine plus oxaliplatin (XELOX) in first-line treatment of metastatic colorectal cancer: a randomized phase II trial of the Swiss Group for Clinical Cancer Research SAKK. Annals of Oncology , 19, 1288-1292. • Borrell-Pages, M., Rojo, F., Albanell, J., Baselga, J., & Arribas, J. (2003. TACE is required for the activation of the EGFR by TGF-α in tumors. EMBO J. , 22, 1114-1124. • Cappuzzo, F., Varella-Garcia, M., Finocchiaro, G., Skokan, M., Gajapathy, S., Carnaghi, C., et al. (2008. Primary resistance to cetuximab therapy in EGFR FISH-positive colorectal cancer patients. British Journal of Cancer , 99, 83 -89. • Capussotti, L., Ferrero, A., Vigano, L., Ribero, D., Lo Tesoriere, R., & Polastri, R. (2006). Major liver resections syncronous with colorectal surgery. Annals of Surgical Oncology , 14, 195-201. • Capussotti, L., Ferrero, A., Vigano, L., Ribero, D., Lo Tesoriere, R., & Polastri, R. (2007). Timing of resection of liver metastases syncronous to colorectal tumor: proposal of prognosis-based decisional mode. Annals of Surgical Oncology , 14, 1143-1150. • Carter, P. (2001. Improving the efficacy of antibody-based cancer therapies.Nature Rev. Cancer , 1, 118-129.• Cemazar, M., Golzio, M., Sersa, G., Rols, M., & Teissie, J. ( 2006). Electricallyassisted nucleic acids delivery to tissues in vivo: where do we stand? Curr Pharm Des , 12, 3817-3825. • Chabner, B., & Roberts, T. (2005, january). Chemotherapy and the war on cancer. Nature reviews , 5, pp. 65-72.• Chan, T., Rittenhouse, S., & Tsichlis, P. (1999). AKT/PKB and other D3 phosphoinositide-regulated kinases: kinase activation by phosphoinositidedependent phosphorylation. Annu. Rev. Biochem. , 68, 965-1014. • Cho, H. S. (2003. Structure of the extracellular region of HER2 alone and in complex with the Herceptin Fab. Nature , 421, 756-760.• Chou, J.-L., Fan, Z., DeBlasio, T., Ko, A., Rosen, N., & Mendelsohn, J. (1999).Constitutive overexpression of cyclin D1 in human breast epithelial cells does not prevent G1 arrest induced by deprivation of epidermal growth factor. Breast Cancer Res. Treat. , 55, 267-283. • Chu, E. (2008, May). Molecular Biomarker Development for Anti-EGFR Therapy: Moving Beyond EGFR Expression. Clinical Colorectal Cancer , 162.• Chung, K., Shia, J., Kemeny, N., & al. (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, 1803-1810. • Ciardiello, F., Bianco, R., Damiano, V., & al. (2000. Antiangiogenic and antitumor activity of anti-epidermal growth factor receptor C225 monoclonal antibody in combination with vascular endothelial growth factor antisense oligonucleotide in human GEO colon cancer cells. Clin Cancer Res , 6 (9), 3739-3747.• Ciardiello, F., Bianco, R., Damiano, V., & al. (1999). Antitumor activity of sequential treatment with topotecan and anti-epidermal growth factor receptor monoclonal antibody C225. Clin Cancer Res , 5, 909-916. • Ciardiello, F., Caputo, R., Bianco, R., & al. (2001). Inhibition of growth factor production and angiogenesis in human cancer cells by ZD1839 ('Iressa'), a selective epidermal growth factor receptor tyrosine kinase inhibitor. Clin Cancer Res , 7, 1459-1465.• Ciardiello, F., Damiano, V., De Lorenzo, S., & al. (1999). Antitumor activity of sequential treatment with topotecan and anti-epidermal growth factor receptor antibody. Clin Cancer Res , 5, 909-916. • Citri, A., & Yarden, Y. (2006). EGF-ERBB signalling: towards the systems level. Nature reviews , 7, 505-516.• Clynes, R. A., Towers, T. L., Presta, L. G., & Ravetch, J. V. (2000). Inhibitory Fc receptors modulate in vivo cytoxicity against tumor targets. Nature Med , 6, 443-446. • Cohen, J. (1995). IL-12 deaths: explanation and a puzzle. Science , 270, 208.• Cohen, R., Falcey, J., Paulter, V., Fetzer, K., & Waksal, H. (2000). Safety profile of the monoclonal antibody (MOAB) IMC-C225, an anti-epidermal growth factor receptor (EGFR) used in the treatment of EGFR-positive tumors. Proc Am Soc Clin Oncol , 1862.• Coinaud, C. (1957). Le fois-etudes anatomiques et chirurgicales. Paris: Masson.• Colucci, G., Giuliani, F., Mattioli, R., & al. (2006). FOLFOX-4 + Cetuximab in untreated patients with advanced colorectal cancer. A phase II study of the Gruppo Oncologico dell'Italia Meridionale (prot. GOIM 2402). J Clin Oncol , 24, 18S.• Cunningham, D., Humblet, Y., Siena, S., & al. (2004). Cetuximab monotherapy and Cetuximab plus Irinotecan in Irinotecan-refractory metastatic colorectal cancer. N Engl J Med , 351, 337-345. • Dakhil, S., Cosgriff, T., Headley, D., & al. (2006). Cetuximab + FOLFOX-6 as first line therapy for metastatic colorectal cancer (An International Oncology Network study, I-03-002). J Clin Oncol , 24, 18s.• Di Nicolantonio, F., Martini, M., Molinari, F., Sartore-Bianchi, A., Arena, S., Saletti, P., et al. (2008). Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer. J Clin Oncol. , 26 (35), 5668-5670. • Di Renzo, F., Olivero, M., Giacomini, A., Porte, H., Chastre, E., Mirossay, L., et al. (1995). Overexpression and amplification of Met/HGF receptor gene during the progression of colorectal cancer. Clin Cancer Res , 1, 147-154.• Dillman, R., Johnson, D., Shawler, D., & Koziol, J. (1988). Superiority of an acid-labile daunorubicin-monoclonal antibody immunoconjugate compared to free drug. Cancer Res. (48), 6097-6102.• Divgi, C., Welt, C., Kris, M., & al. (1991). Phase I and imaging trial of indium-111 labeled anti-EGF receptor monoclonal antibody 225 in patients with squamous cell lung carcinoma. J Natl Cancer Inst , 83, 97-104.• Douillard, J., Cunningham, D., Roth, A., & al. (2000). Irinotecan combined with Fluorouracil compared with Fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicenter randomized trial. Lancet , 355, 1041-1047.• Dowell, J., & Minna, J. ( 2004). The impact of epidermal-growth-factor-receptor mutations in response to lung-cancer therapy. Nat Clin Pract Oncol , 1, 2-3.• Durai, R., Yang, S., Seifalian, A., & Winslet, M. (2008). Principles and Applications of Gene Therapy in Colon Cancer. J Gastrointestin Liver Dis , 17(1), 59-67.• Eberhard, D., Johnson, B., Amler, L., & al. (2005). Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-small-cell lung cancer treated with chemotherapy alone and in combination with erlotinib. J Clin Oncol , 23, 5900-5909.• Ekstrand, A. J., Sugawa, N., James, C. D., & Collins, V. P. (1992). Amplified and rearranged epidermal growth factor receptor genes in human glioblastomas reveal deletions of sequences encoding portions of the N-and/or C-terminal tails. Proc. Natl Acad. Sci. USA , 89, 4309-4313. • Eng, C., Maurel, J., Scheithauer, W., & al. (2007). Impact of quality of life of adding Cetuximab to irinotecan in patients who have failed prior oxaliplatinbased therapy: the EPIC trial. J Clin Oncol , 25, 164.• Evan, G., Wyllie, A., Gilbert, C., Littlewood, T., Land, H., Brooks, M., et al. (1992). Induction of apoptosis in fibroblasts by c-myc protein. Cell , 69, 119-128. • Franklin, M. C., & al, e. (2004). Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex. Cancer Cell , 5, 317-328. • Fry, D. (2000). Site-directed irreversible inhibitors of the erbB family tyrosine kinases as novel chemotherapeutic agents for cancer. Anticancer Drug Res , 15, 3-16.• Fueyo, J., Gomez-Manzano, C., Alemany, R., Lee, P., McDonnell, T., Mitlianga, P., et al. (2000). A mutant oncolytic adenovirus targeting the Rb pathway produces anti-glioma effect in vivo. Oncogene , 19, 2-12.• Fujita, S., & Sugano, K. (1997). Expression of c-Met protooncogene in primary colorectal cancer and liver metastases. Jpn J Clin Oncol , 27 (6), 378-383. • Fuks, D., Cook, M., Brehant, O., Henegar, A., Dumont, F., Chatelain, D., et al. (2008). Colorectal carcinoma with potentially resectable metastases: factors associated with the failure of curative schedule. Gastroenterol Clin Biol , 32 (4), 390-400.• Fukuoka, M., Yano, S., Giaccone, G., & al, e. (2003). Multi-institutional randomized phase II trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer. J Clin Oncol , 21, 2237-2246. • Garnett, M. (2001. Targeted drug coniugates: principles and progress.  Cell. , 11, 495-505. • Gatzemeier, U., Pluzanska, A., Szczesna, A., & al. (2004). Results of a phase III trial of erlotinib (OSI-774) combined with cisplatin and gemcitabine (GC) chemotherapy in advanced non-small cell lung cancer (NSCLC). ASCO Meeting Abstracts , 22, 7010.• Giaccone, G., Herbst, R., Manegold, C., & al, e. (2004). Gefitinib in combination with gemcitabine and cisplatin in advanced non-small-cell lung cancer: A phase III trial-INTACT 2. J Clin Oncol , 22, 777-784. • Gill, G., Kawamoto, T., Cochet, C., Le, A., Sato, J., Masui, H., et al. (1984).Monoclonal anti-epidermal growth factor receptor antibodies which are inhibitors of epidermal growth factor binding and antagonists of epidermal growth factor binding and antagonists of epidermal growth factor-stimulated tyrosine protein kinase activity. J. Biol. Chem. , 259, 7755-7760. • Gillies, S. D. (1993). Biological activity and in vivo clearance of antitumor antibody/cytokine fusion proteins. Bioconjug. Chem. , 4, 230-235. • Gillies, S. D. (1991). Expression of genetically engineered immunoconjugates of lymphotoxin and a chimeric anti-ganglioside GD2 antibody. Hybridoma , 10, 347-356.• Goldstein, N., Prewett, M., Zuklys, K., Rockwell, P., & J., M. (1995). Biological • Heise, C., Hermiston, T., Johnson, L., Brooks, G., Sampson-Johannes, A., Williams, A., et al. (2000). An adenovirus E1A mutant that demonstrates potent and selective systemic anti-tumoral effi cacy. Nat Med , 6, 1134-1139. • Hemming, A., Reed, A., Howard, R., Fujita, S., & Hochwald, S. (2003.Preoperative Portal Vein Embolization for Extended Hepatectomy. Annals of Surgery , 237 (5), 686-693. • Herbst, R., & Shin, D. (2002). Monoclonal antibodies to target epidermal growth factor receptor -positive tumors. A new paradigm for cancer therapy. American Cancer Society , 94 (5), 1593-1611.• Herbst, R., Giaccone, G., Schiller, J., & al. (2004). Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: A phase III trial-INTACT 2. J Clin Oncol , 22, 785-794.• Herbst, R., Kim, E., & Harari, P. (2001). IMC-C225, an anti-epidermal growth factor receptor monoclonal antibody, for treatment of head and neck cancer.Expert Opin Biol Ther , 1, 719-732.• Herbst, R., Prager, D., Hermann, R., & al. (2005) • Hirsch, F., Varella-Garcia, M., McCoy, J., & al. (2005). Increased epidermal growth factor receptor gene copy number detected by fluorescence in situ hybridization associates with increased sensitivity to gefitinib in patients with bronchioloalveolar carcinoma subtypes: A Southwest Oncology Group Study. J Clin Oncol , 23, 6838-6845. • Holbro, T., & Hynes, N. E. (2004). ErbB receptors: directing key signaling networks throughout life. Annu. Rev. Pharmacol.Toxicol. , 44, 195-217. • Hoogenboom, H. R. (1991). Construction and expression of antibody-tumor necrosis factor fusion proteins. Mol. Immunol. , 98, 1027-1037. • Huang, S. (1999. Gene expression profiling, genetic networks, and cellular states: an integrating concept for tumorigenesis and drug discovery. J Mol Med , 77, 469-480.• Huang, S., Armstrong, E., Benavente, S., & al, e. (2004). Dual-agent molecular targeting of the epidermal growth factor receptor (EGFR): Combining anti-EGFR antibody with tyrosine kinase inhibitor. Cancer Res , 64, 5355-5362. • Huang, S., Bock, J., & Harari, P. (1999). Epidermal growth factor receptor blockade with C225 modulates proliferation, apoptosis, and radiosensitivity blockade with C225 modulates proliferation, apoptosis, and radiosensitivity in squamous cell carcinomas of the head and neck. Cancer Res , 59, 1935-1940. • Hudziak, R. M., & al., e. (1989. p185HER2 monoclonal antibody has antiproliferative effects in vitro and sensitizes human breast tumor cells to tumor necrosis factor. Mol. Cell. Biol. , 9, 1165-1172. • Hurwitz, H. e. (2004. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med , 350, 2335-2342. • Hynes, N. E., & Stern, D. F. (1994. The biology of erbB-2/neu/HER-2 and its role in cancer. Biochim. Biophys. Acta , 1198, 165-184. • Hynes, N., & Lane, H. (2005. ERBB receptors and cancer: the complexity of targeted inhibitors. Nature reviews , 5, 341-354.• Imperiale, T. (2003). Aspirin and the prevention of colorectal cancer. N Engl J Med , 348, 879.• Inoue, K., Shuin, T., Hicklin, D., & al. (2000). Paclitaxel enhances the effect of treatment of metastatic human transitional cell carcinoma with the anti-epidermal growth factor receptor monoclonal antibody C225. Proc Am Assoc Cancer Res , 41, 529.• Ishizawar, R., & Parsons, S. J. ( 2004). c-Src and cooperating partners in human cancer. Cancer Cell , 6, 209-214. • Jackson, J. G., St Clair, P., Sliwkowski, M. X., & Brattain, M. G. (2004).Blockade of epidermal growth factor-or heregulin-dependent ErbB2 activation with the anti-ErbB2 monoclonal antibody 2C4 has divergent downstream signaling and growth effects. Cancer Res. , 64, 2601-2609.• Janmaat, M. L., Kruyt, F. A., Rodriguez, J. A., & Giaccone, G. (2003). Response to epidermal growth factor receptor inhibitors in non-small cell lung cancer cells: limited antiproliferative effects and absence of apoptosis associated with persistent activity of extracellular signal-regulated kinase or Akt kinase pathways.Clin. Cancer Res. , 9, 2316-2326. • Janne, P. (2004 Cancer Res. , 47, 3118-3122. • Johnson, J., & al. (1981). A vindesine-anti-CEA coniugate cytotoxic for human cancer cells in vitro. Br. J. Cancer (44).• Jonker, D., O'Callaghan, C., Karapetis, C., Zalcberg, J., Tu, D., Au, H., et al. (2007). Cetuximab for the Treatment of Colorectal Cancer. N Engl J Med , 357, 2040-2048. • Kaelin, W. (2005. The concept of synthetic lethality in the context of anticancer therapy. Nat Rew Cancer , 5, 689-698.• Karapetis, C., Khambata-Ford, S., Jonker, D., & al. (2008). K-ras mutations and benefit from Cetuximab in advanced colorectal cancer. N Engl J Med , 359, 1757-1765. • Kario, E. e. (2005. Suppressors of cytokine signaling 4 and 5 regulate epidermal growth factor receptor signaling. J. Biol. Chem. , 280, 7038-7048. • Karmali, P., & Chaudhuri, A. (2007). Cationic liposomes as non-viral carriers of gene medicines: resolved issues, open questions, and future promises. Med Res Rev , 27, 696-722. • Karunagaran, D., Tzahar, E., Beerli, R., Chen, X., Graus-Porta, D., Ratzkin, B., et al. (1996). ErbB-2 is a common auxiliary subunit of NDF and EGF receptors: implications for breast cancer. EMBO J. , 15, 254-264. • Kasper, Braunwald, Fauci, Hauser, Longo, & Jameson. (2005). Harrison-Principi di medicina interna (16 ed., Vol. 1). Mc Graw Hill.• Kawamoto, T., Sato, J., Le, A., Poliko, J., Sato, G., & Mendelsohn, J. (1983).Growth stimulation of A431 cells by epidermal growth factor: identification of high-affinity receptors for epidermal growth factor by an anti-receptor monoclonal antibody. Proc. Natl. Acad. Sci. USA , 80, 1337-1341. • Keilholz, U. e. (1997. Recombinant interleukin-2-based treatments for advanced melanoma: the experience of the European Organization for Research and Treatment of Cancer Melanoma Cooperative Group. Cancer J. Sci. Am. , 3 (Suppl. 1), S22-S28.• Kemeny, M., Adak, S., Gray, B., & al. (2002). Combined-modality treatment for resectable metastatic colorectal carcinoma to the liver: surgical resection of hepatic metastases in combination wiyh continous infusion of chemotherapy-an Intergroup study. J Clin Oncol , 20, 1499-1505. • Kemeny, N., & Gonen, M. (2005. Hepatic arterial infusion after liver resection.N Engl J Med , 352, 734-735. • Kerbel, R., & Folkman, J. (2002). Clinical translation of angiogenesis inhibitors.Nature Rev. Cancer , 2, 727-739. • Kerr, D. (2003). Clinical development of gene therapy for colorectal cancer.Nature reviews , 3, 615-622.• Kerr, J. e. (1994). Apoptosis. Its significance in cancer and cancer therapy. , 73, 2013-2026. • Khambata-Ford, S., Garrett, C., Meropol, N., Basik, M., Harbison, C., Wu, S., et al. (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), 3230-3237. • Khatri, V., Petrelli, N., & Belghiti, J. (2005). Extending the frontiers of surgical therapy for hepatic colorectal metastases: is there a limit? J Clin Oncol , 23, 8490-9.