Signaling multiplex of the epidermal growth factor receptor

References

• Aroian RV, Sternberg PW. Multiple functions of let-23, a Caenorhabditis elegans receptor tyrosine kinase gene required for vulval induction. Genetics 128,251–267 (1991).
   PubMedGoogle Scholar
• Schweitzer R, Howes R, Smith R, Shilo BZ, Freeman M. Inhibition of Drosophila EGF receptor activation by the secreted protein Argos. Nature 376,699–702 (1995).
   Google Scholar
• Salomon DS, Brandt R, Ciardiello F, Normanno N. Epidermal growth factor-related peptides and their receptors in human malignancies. Crit. Rev. Oncol. HematoL 19,183–232 (1995).
   PubMed Web of Science ®Google Scholar
• Harris AL, Nicholson S, Sainsbury R, Wright C, Farndon J. Epidermal growth factor receptor and other oncogenes as prognostic markers. Natl Cancer Inst. Monogr. 11,181–187 (1992).
   Google Scholar
• Wong AJ, Bigner SH, Bigner DD, Kinzler KW, Hamilton SR, Vogelstein B. Increased expression of the EGF receptor gene in malignant gliomas is invariably associated with gene amplification. Proc. Natl Acad. Sci. 84,6899–6903 (1987).
   PubMed Web of Science ®Google Scholar
• Korc M, Chandrasekar B, Yamanaka Y, Friess H, Buchier M, Beger HG. Overexpression of the epidermal growth factor receptor in human pancreatic cancer is associated with concomitant increases in the levels of epidermal growth factor and transforming growth factor-a. J Invest. 90,1352–1360 (1993).
   Google Scholar
• Schlessinger J. Cell signaling by receptor tyrosine kinases. Cell 103,211–225 (2000).
   PubMed Web of Science ®Google Scholar
• Riese DJ II, Stern DE Specificity within the EGF family/ErbB receptor family signaling network. Bioessays 20,41–48 (1998).
   PubMedGoogle Scholar
• Graus-Porta D, Beerli RR, Daly JM, Hynes NE. ErbB-2, the preferred heterodimerization partner of all ErbB receptors, is a mediator of lateral signaling. EMBO J 16,1647–1655 (1997).
   Google Scholar
• •• Provocative evidence that erbB receptors have distinct signaling properties depending on dimization partner.
   Google Scholar
• Guy PM, Platko JV, Cantley LC, Cerione RA, Carraway KL. Insect cell-expressed p180ERB3 possesses an impaired tyrosine kinase activity. Proc. Natl Acad. Sci. 91,8132-8136 (1994). iiMiettinen PJ, Berger JE, Meneses J et al. Epithelial immaturity and multiorgan failure in mice lacking epidermal growth factor receptor. Nature 376,337–341 (1995).
   Google Scholar
• Lee KF, Simon H, Chen H, Bates B, Hung MC, Hauser C. Requirement for neuregulin receptor erbB2 in neural and cardiac development. Nature 378, 394–398 (1995).
   PubMed Web of Science ®Google Scholar
• Jones FE, Stern DE Expression of dominant-negative ErbB2 in the mammary gland of transgenic mice reveals a role in lobuloaveolar development and lactation. Oncogene 18,3481–3490 (1999).
   PubMed Web of Science ®Google Scholar
• Jones FE, Welte T, Fu XY, Stern DE ErbB4 signaling in the mammary gland is required for lobuloalveolar development and Stat5 activation during lactation. J Cell Biol. 147,77–87 (1999).
   PubMed Web of Science ®Google Scholar
• Luetteke NC, Qiu TH, Peiffer RL, Oliver P, Smithies O, Lee DC. TGFa deficiency results in hair follicle and eye abnormalities in targeted and waved-1 mice. Ce1173, 263–278 (1993).
   Google Scholar
• Mann GB, Fowler KJ, Gabriel A, Nice EC, Williams RL, Dunn AR. Mice with a null mutation of the TGF-a gene have abnormal skin architecture, wavy hair, and curly whiskers and often develop corneal inflammation. Cell 73, 249–261 (1993).
   PubMed Web of Science ®Google Scholar
• Sibilia M, Steinbach JP, Stingl L, Aguzzi A, Wagner EF. A strain-dependent postnatal neurodegeneration in mice lacking EGF receptor. EMBO J 17, 719–731 (1998).
   Google Scholar
• •Striking differences observed in epidermal growth factor receptor (EGFR) -knockout mice.
   Google Scholar
• Lax I, Burgess WH, Bellot F, Ullrich A, Schlessinger J, Givol D. Localization of a major receptor-binding domain for epidermal growth factor by affinity labeling. MoL Cell. Biol. 8,1831–1834 (1988).
   PubMedGoogle Scholar
• Lax I, Bellot F, Howk R, Ullrich A, Givol D, Schlessinger J. Functional analysis of the ligand binding site of EGF-receptor utilizing chimeric chicken/human receptor molecules. EMBOJ 8,421–427 (1989).
   PubMed Web of Science ®Google Scholar
• Ogiso H, Ishitani R, Nureki O et al. Crystal structure of the complex of human epidermal growth factor and receptor extracellular domains. Cell 110, 775–787 (2002).
   PubMed Web of Science ®Google Scholar
• ••Important findings elucidated by theEGFR crystal structure.
   Google Scholar
• Wiesmann C, Fuh G, Christinger HW, Eigenbrot C, Wells JA, de Vos AM. Crystal structure at 1.7 A resolution of VEGF in complex with domain 2 of the Flt-1 receptor. Cell 91,695–704 (1997).
   Google Scholar
• Garrett TPJ, McKern NM, Lou M et al. Crystal structure of a truncated epidermal growth factor receptor extracellular domain bound to transforming growth factor-a. Ce11110, 763–773 (2002).
   Google Scholar
• ••Important findings of the EGFR crystalstructure simultaneously reported to [20].
   Google Scholar
• Olayioye MA, Graus-Porta D, Beerli RR, Rohrer J, Gay B, Hynes NE. ErbB-1 and erbB-2 acquire distinct signaling properties dependent upon their dimerization partner. Mol. Cell. Biol. 18,5042-5051 (1998).
   Google Scholar
• Alroy I, Yarden Y. The ErbB signaling network in embryogenesis and oncogenesis: signal diversification through combinatorial ligand-receptor interactions. FEBS Lett. 410,83–86 (1997).
   PubMed Web of Science ®Google Scholar
• Gamett DC, Pearson G, Cerione RA, Friedberg I. Secondary dimerization between members of the epidermal growth factor receptor family. J Biol. Chem. 272, 12052–12056 (1997).
   PubMed Web of Science ®Google Scholar
• Hirsch FR, Varella-Garcia M, Franklin WA et al. Evaluation of HER-2/neu gene amplification and protein expression in non-small cell lung carcinomas. Br. J Cancer86, 1449–1456 (2002).
   Google Scholar
• Tzahar E, Waterman H, Chen X et al. A hierarchical network of inter-receptor interactions determines signal transduction by Neu differentiation factor/neuregulin and epidermal growth factor. Mol. Cell. Biol. 16,5276–5287 (1996).
   PubMed Web of Science ®Google Scholar
• Hughes DPM, Thomas DG, Giordano TJ, Baker LH, McDonagh KT. Cell surface expression of epidermal growth factor receptor and Her-2 with nuclear expression of Her-4 in primary osteosarcoma. Cancer Res. 64,2047-2053 (2004).
   Google Scholar
• Takai Y, Sasaki T, Matozaki T. Small GTP-binding proteins. Physiol. Rev. 81, 153–208 (2001).
   Google Scholar
• Johnson L, Greenbaum D, Cichowski K et al. K-ras is an essential gene in the mouse with partial functional overlap with N-ras. Genes Dev. 11,2468–2481 (1997).
   PubMed Web of Science ®Google Scholar
• Koch AC, Anderson D, Moran MF, Ellis C, Pawson T. SH-2 and SH-3 domains: elements that control interactions of cytoplasmic signaling proteins. Science 252, 668–674 (1991).
   Google Scholar
• Avruch J, Khokhlatchev A, Kyriakis JM et al. Ras activation of the Raf kinase: tyrosine kinase recruitment of the MAPK cascade. Recent Prog. Horm. Res. 56,127–155 (2001).
   PubMedGoogle Scholar
• Chang F, Lee JT, Navolanic PM et al. Involvement of PI3K/Akt pathway in cell cycle progression, apoptosis, and neoplastic transformation: a target for cancer chemotherapy. Leukemial7, 590–603 (2003).
   Google Scholar
• •Comprehensive review of the phosphatidylinositol-3 -kinase (PI3K)/Akt pathway.
   Google Scholar
• Martinez-Lorenzo MJ, Anel A, Monleon I et al. Tyrosine phosphorylation of the p85 subunit of phosphatidylinositol 3-kinase correlates with high proliferation rates in sublines derived from the Jurkat leukemia. Int. J Biochem. Cell. Biol. 32,435-445 (2000).
   Google Scholar
• Datta SR, Dudek H, Tao X et al. Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Ce1191, 231–241 (1997).
   Google Scholar
• Franke TF, Kaplan DR, Cantley LC. PI3K: downstream AKTion blocksapoptosis. Ce1188, 435–437 (1997).
   Google Scholar
• Scott PH, Brunn GJ, Kohn AD et al. Evidence insulin-stimulated phosphorylation and activation of the mammalian target of rapamycin mediated by a protein kinase B signaling pathway. Proc. Natl Acad. Sd. 95,7772–7777 (1998).
   PubMed Web of Science ®Google Scholar
• Jiang B-H, Zheng JZ, Aoki M, Vogt PK. Phosphatidylinositol 3-kinase signaling mediates angiogenesis and expression of vascular endothelial growth factor in endothelial cells. Proc. Natl Acad. Sci. 97, 1749–1753 (2000).
   Google Scholar
• Jorissen RN, Walker F, Pouliot N, Garrett TP, Ward CW, Burgess AW. Epidermal growth factor receptor: mechanisms of activation and signaling. Exp. Cell Res. 284,31–53 (2003).
   PubMed Web of Science ®Google Scholar
• Ahonen TJ, Xie J, LeBaron MJ et al. Inhibition of transcription factor Stat5 induces cell death of human prostate cancer cells. J Biol. Chem. 278, 27287–27292 (2003).
   Google Scholar
• Burke P, Schooler K, Wiley HS. Regulation of epidermal growth factor receptor signaling by endocytosis and intracellular trafficking. Mo/. Biol. Ce1112, 1897–1910 (2001).
   Google Scholar
• Robertson KW, Reeves JR, Smith G et al. Quantitative estimation of epidermal growth factor receptor and c-erb-2 in human breast cancer. Cancer Res. 56, 3823–3830 (1996).
   PubMedGoogle Scholar
• Irish JC, Bernstein A. Oncogenes in head and neck cancer. Laryngoscope 103, 42–52 (1993).
   PubMed Web of Science ®Google Scholar
• Fontanini G, Vignati S, Bigini D et al. Epidermal growth factor receptor (EGFr) expression in non-small cell lung carcinomas correlates with metastatic involvement of hilar and mediastinal lymph nodes in the squamous subtype. Eur. Cancer31A, 178–183 (1995).
   PubMedGoogle Scholar
• Wong AJ, Ruppert, Bigner SH et al. Structural alterations of the epidermal growth factor receptor gene in human gliomas. Proc. Natl Acad. Sci. 89, 2965–2969 (1992).
   PubMed Web of Science ®Google Scholar
• Di Marco E, Pierce JH, Fleming TP et al. Autocrine interaction between TGF-a and the EGF-receptor: quantitative requirements for induction of the malignant phenotype. Oncogene 4, 831–838 (1992).
   Google Scholar
• Hanahan D, Weinbert RA. The hallmarks of cancer. Cell 100,57–70 (2000).
   PubMed Web of Science ®Google Scholar
• •Excellent review of critical traits in tumorigenesis.
   Google Scholar
• Todaro GJ, De Larco JE. Growth factors produced by sarcoma virus-transformedcells. Cancer Res. 38,4147–4154 (1978).
   PubMed Web of Science ®Google Scholar
• •First report of autocrine and paracrine pathways utilized by tumor cells.
   Google Scholar
• Gimbrone MA, Leapman SB, Cotran RS, Folkman J. Tumor dormancy in vivoby prevention of neovascularization. J Exp. Med. 136,261–276 (1972).
   PubMed Web of Science ®Google Scholar
• Garcia-Barros M, Paris F, Cordon-Cardo C et al. Tumor response to radiotherapy regulated by endothelial cell apoptosis. Science 300,1155–1159 (2003).
   PubMed Web of Science ®Google Scholar
• Bruns CJ, Solorzano CC, Harbison MT et al. Blockade of the epidermal growth factor receptor signaling by a novel tyrosine kinase inhibitor leads to apoptosis of endothelial cells and therapy of human pancreatic carcinoma. Cancer Res. 60, 2926–2935 (2000).
   PubMed Web of Science ®Google Scholar
• Rak J, Mitsuhashi Y, Sheehan C et al. Oncogenes and tumor angiogenesis: differential modes of vascular endothelial growth factor upregulation in ras-transformed epithelial cells and fibroblasts. Cancer Res. 60,490–498 (2000).
   PubMed Web of Science ®Google Scholar
• Vitoria Petit AM, Rak J, Hung M-C et al. Neutralizing antibodies against epidermal growth factor and erbB-2/neu receptor tyrosine kinases downregulate vascular endothelial growth factor production by tumor cells in vitro and in vivo. Am. J Pathol. 151,1523-1530 (1997).
   Google Scholar
• Wang D, Su Huang H-J, Kazlauskas A, Cavenee WK. Induction of vascular endothelial growth factor expression in endothelial cells by platelet-derived growth factor through the activation of phosphatidylinositol 3-kinase. Cancer Res. 59,1464-1472 (1999).
   Google Scholar
• Pidgeon GP, Barr MP, Harmey JH, Foley DA, Bouchier-Hayes DJ. Vascular endothelial growth factor (VEGF) upregulates bc1-2 and inhibits apoptosis in human and murine mammary adenocarcinoma cells. Br. J Cancer 85, 273–278 (2001).
   Google Scholar
• Katoh O, Takahashi T, Oguri T et al. Vascular endothelial growth factor inhibits apoptotic death in hematopoietic cells after exposure to chemotherapeutic drugs by inducing MCL1 acting as an anti-apoptotic factor. Cancer Res. 58,5565–5569 (1998).
   PubMed Web of Science ®Google Scholar
• Dias S, Choy M, Alitalo K, Rafii S. Vascular endothelial growth factor (VEGF)- C signaling through FLT-4 (VEGFR3) mediates leukemic cell proliferation, survival, and resistance to chemotherapy. B/ood99,2179–2184 (2002).
   Google Scholar
• •Excellent paper of the potential role of angiogenesis factors in hematologic malignancies.
   Google Scholar
• Ellis RE, Yuan JY, Horvitz HR. Mechanisms and functions of cell death. Ann. Rev. Cell Bio1.7, 663–698 (1991).
   Google Scholar
• Mapara MY, Bargou R, Zugck C et al. APO-1 mediate apoptosis or proliferation in human chronic B lymphocytic leukemia: correlation with bc1-2 oncogene expression. Eur. j I17717711fla 23,702–708 (1993).
   Google Scholar
• Madrid LV, Wang CY, Guttridge DC, Schottelium AJ, Baldwin AS Jr, Mayo MW. Akt suppresses apoptosis by stimulating the transactivation potential of the Re1A/p65 subunit of NF-KB. Mol. Cell. Biol. 20, 1626–1638 (2000).
   Google Scholar
• Sorkin A, McKinsey T, Shih W Kirchhausen T, Carpenter G. Stoichiometric interaction of the epidermal growth factor receptor with the clathrin-associated protein complex AP-2. J. Biol. Chem. 270,619-625 (1995).
   Google Scholar
• Sunada H, Magun BE, Mendelsohn J, MacLeod CL. Monoclonal antibody against epidermal growth factor receptor is internalized without stimulating receptor phosphorylation. Proc. Natl Acad. Sci. 83, 3825–3829 (1986).
   PubMed Web of Science ®Google Scholar
• Wu X, Rubin M, Fan Z et al. Involvement of p27[K 1P 1] in G1 arrest mediated by an anti-epidermal growth factor receptor monoclonal antibody. Oncogene 12, 1397–1403 (1996).
   PubMed Web of Science ®Google Scholar
• Shin DM, Donato NJ, Cooper M et al. Epidermal growth factor receptor-targeted therapy with C225 and cisplatin in patients with head and neck cancer. Clin. Cancer Res. 7, 1204–1213 (2001).
   Google Scholar
• Cunningham D, Humblet Y, Siena S et al. Cetuximab (C225) alone or in combination with irinotecan (CPT-11) in patients with epidermal growth factor receptor (EGFR)-positive, irinotecan refractory metastatic colorectal cancer (MCRC). Proc. Am. Soc. Clin. Oncol. 22 (2003) (Abstract 1012).
   Google Scholar
• Saltz LB, Meropol NJ, Loehrer PJ Sr, Needle MN, Kopit J, Mayer RJ. Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor. J Clin. Oncol. 22,1201–1208 (2004).
   PubMed Web of Science ®Google Scholar
• Rosenberg AH, Loehrer PJ, Needle MN, Waksal H, Hollywood E. Erbitux (IMC-C225) plus weekly irinotecan (CPT-11), fluorouracil (5FU) and leucovorin (LV) in colorectal cancer (CRC) that expresses the epidermal growth factor receptor (EGFr). Proc. Am. Soc. Clin. Oncol. 21(2002) (Abstract 536).
   Google Scholar
• Harari PM, Huang SM. Head and neck cancer as a clinical model for molecular targeting of therapy: combining EGFR blockade with radiation. Int. J Radiat. Oncol. Biol. Phys. 49,427–433 (2001).
   PubMed Web of Science ®Google Scholar
• Fukuoka M, Yano S, Giaccone G et al. 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 (2003).
   PubMed Web of Science ®Google Scholar
• Kris MG, Natale RB, Herbst RS et al. Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer: a randomized trial. JAMA 290,2149–2158 (2003).
   PubMed Web of Science ®Google Scholar
• Giaccone F, Herbst RS, Manegold C et al. Gefitinib in combination with gemcitabine and cisplatin in advanced non-small cell lung cancer: a Phase III trial—INTACT 1. Clin. Oncol. 22,777-784 (2004).
   Google Scholar
• Herbst RS, Giaccone G, Schiller JH et al. Gefitinib in combination with paclitaxel and carboplatin in advanced non-small cell lung cancer: a Phase III trial—INTACT 2. Clin. Oncol. 22,785-794 (2004).
   Google Scholar
• Shepherd FA, Pereira J, Ciuleanu TE et al. A randomized placebo-controlled trial of erlotinib in patients with advanced non-small cell lung cancer (NSCLC) following failure of 1st line or 2nd line chemotherapy. A National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) trial. Proc. Am. Soc. Oncol. 22 (2004) (Abstract 7022).
   Google Scholar
• Hurwitz H, Fehrenbacher T, Cartwright J et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl. J Med. 350, 2335–2342 (2004).
   PubMed Web of Science ®Google Scholar
• •Results of the pivotal trial showing the survival benefits in patients receiving antiangiogenesis therapy.
   Google Scholar
• Overholser JP, Prewett MC, Hooper AT, Waksal HW, Hicklin DJ. Epidermal growth factor receptor blockage by antibody IMC-C225 inhibits growth of a human pancreatic carcinoma xenograft in nude mice. Cancer 89,74–82 (2000).
   Google Scholar
• Inoue K, Slaton JVV, Perrotte P et al. Paclitaxel enhances the effects of the anti-epidermal growth factor receptor antibody monoclonal antibody Imclone C225 in mice with metastatic human bladder transitional cell carcinoma. Clin. Cancer Res. 6,4874-4884 (2000).
   Google Scholar
• Humphrey PA, Wong AJ, Vogelstein B et al. Amplification and expression of the epidermal growth factor receptor gene in human glioma xenografts. Cancer Res. 48, 2231–2238 (1988).
   PubMed Web of Science ®Google Scholar
• Sugawa N, Ekstrand AJ, James CD, Collins VP Identical splicing of aberrant epidermal growth factor receptor transcripts from amplified rearranged genes in human glioblastomas. Proc. Natl Acad. St.]. 87,8602–8606 (1990).
   PubMed Web of Science ®Google Scholar
• Moscatello DK, Holgado-Madruga M, Godwin AK et al. Frequent expression of a mutant epidermal growth factor receptor in multiple human tumors. Cancer Res. 55, 5536–5539 (1995).
   PubMed Web of Science ®Google Scholar
• Su Huang HJ, Nagane M, Klingbeil CK et al. The enhanced tumorigenic activity of a mutant epidermal growth factor receptor common in human cancers is mediated by threshold levels of constitutive tyrosine phosphorylation and unattenuated signaling. J Biol. Chem. 272,2927–2935 (1997).
   PubMedGoogle Scholar
• Helm n K, Beguinot L. Internalization and downregulation of the human epidermal growth factor receptor are regulated by the carboxyl-terminus tyrosines. J. Biol. Chem. 266,8363–8368 (1991).
   PubMedGoogle Scholar
• Moulder SL, Yakes FM, Muthuswamy SK, Bianco R, Simpson FJ, Arteaga CL. Epidermal growth factor receptor (HERO tyrosine kinase inhibitor ZD1839 (Iressa) inhibits HER2/neu (erbB2)-overexpressing breast cancer cells in vitro and in vivo. Cancer Res. 61,8887–8895 (2001).
   PubMed Web of Science ®Google Scholar
• •Excellent study and presentation of data.
   Google Scholar
• Wallasch C, WeiB, Niederfellner G, Jallal B, Issing W, Ullrich A. Heregulin-dependent regulation of heR2/neu oncogenic signaling by heterodimerization with heR3. EMBO 14,4267–4275 (1995).
   PubMed Web of Science ®Google Scholar
• Alimandi M, Romano A, Curia MC et al. Co-operative signaling of erbB3 and erbB2 in neoplastic transformation and human mammary carcinomas. Oncogene10, 1813–1821 (1995).
   PubMed Web of Science ®Google Scholar
• Baulida J, Kraus MH, Alimandi M, Di Fiore PP, Carpenter G. All erbB receptors other than the epidermal growth factor receptor are endocytosis impaired. J Biol. Chem. 271,5251–5257 (1996).
   Google Scholar
• ••Notable paper showing the differentialcapacity of downregulating erbB receptors.
   Google Scholar
• Chen YF, Pan GZ, Hou X et al. Epidermal growth factor and its receptors in human pancreatic carcinoma. Pancreas 5, 278–283 (1990).
   PubMedGoogle Scholar
• Slamon DJ, Clark GM, Wong SG et al. Human breast cancer correlation of relapse and survival with amplification of the HER-2/rteu oncogene. Science 235, 177–182 (1987).
   PubMed Web of Science ®Google Scholar
• Lowy DR, Willumsen BM. Function and regulation of ras. Ann. Rev Biochern. 62, 851–891 (1993).
   PubMed Web of Science ®Google Scholar
• Ferguson KM, Darling PJ, Mohan MJ, Macatee TL, Lemmon MA. Extracellular domains drive homo- but not hetero-dimerization of erbB receptors. EMBO 19,4632–4643 (2000).
   Google Scholar
• •• Excellent paper describing the complex interaction between ligand and EGFR.
   Google Scholar
• Gangarosa LM, Sizemore N, Graves-Deal R, Oldham SM, Der CJ, Coffey RJ. A raf-independent epidermal growth factor receptor autocrine loop is necessary for Ras transformation of rat intestinal epithelial cells. J Biol. Chem. 272,18926–18931 (1997).
   Google Scholar
• Nishikawa R, Ji X-D, Harmon RC et al. A mutant epidermal growth factor receptor common in human glioma confers enhanced tumorigenicity. Proc. Natl Acad. Sci. 91,7727–7731 (1994).
   PubMed Web of Science ®Google Scholar
• Frenzel N, Zwick E, Daub H et al. EGF receptor transactivation by G-protein coupled receptors requires metalloproteinase cleavage of proHB-EGE Nature 402,884–888 (1999).
   Google Scholar
• Liu D, Aguirre Ghiso JA, Estrada Y, Ossowski L. EGFR is a transducer of the urokinase receptor initiated signal that is required for in vivo growth of human carcinoma. Cancer Cell 1, 445–457 (2002).
   PubMed Web of Science ®Google Scholar
• Lynch TJ, Bell DW, Sordella R et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small cell lung cancer to gefitinib. N Engl. j Med. 350, 2129–2139 (2004).
   PubMed Web of Science ®Google Scholar
• •• Noteworthy paper describing the molecular aberrations activating EGFR and susceptibility to EGFR tyrosine kinase inhibition.
   Google Scholar
• Sordella R, Bell DW, Haber DA, Settleman J. Gefitinib-sensitizing EGFR mutations in lung cancer activate anti-apoptotic pathways. Science 305, 1163–1167 (2004).
   PubMed Web of Science ®Google Scholar
• ••Exceptional paper following up on theEGFR mutations reported in [94].
   Google Scholar
• Udari M, Utikal J, Krahn GM, Peter RU. Chromosome 7 aneusomy. A marker for metastatic melanoma? Expression of the epidermal growth factor receptor gene and chromosome 7 aneusomy in nevi, primary malignant melanomas and metastases. Neoplasia 3,245–254 (2001).
   Google Scholar
• Singh RK, Tsan R, Radinsky R. Influence of the host microenvironment on the clonal selection of human colon carcinoma cells during primary tumor growth and metastasis. Clin. Exp. Metastasis 15, 140–150 (1997).
   Google Scholar
• Tipping AJ, Mahon FX, Lagarde V, Goldman JM, Melo JV. Restoration of sensitivity to 5T1571 in 5TI571-resistant chronic myeloid leukemia cells. Blood 98, 3864–3867 (2001).
   Google Scholar
• Branford S, Rudzki Z, Walsh S et al. Detection of BCR-ABL mutations in patients with CML treated with imatinib is virtually always accompanied by clinical resistance, and mutations in the ATP phosphate-binding loop (P-loop) are associated with a poor prognosis. Blood 102,276–283 (2003).
   PubMed Web of Science ®Google Scholar