Predicting response to epidermal growth factor receptor-targeted therapy in colorectal cancer

Expert Review of Anticancer Therapy

Volumn 7, Issue 4, 2007, Pages 503-518

  Adams, Richard ^a   Maughan, Tim ^a  

^a VELINDRE CANCER CENTRE   (United Kingdom)

Author keywords

Biological marker; Cetuximab; Colorectal cancer; EGFR; Epidermal growth factor receptor; Erlotinib; Gefitinib; Panitumumab; Predictive marker; Targeted therapy

Indexed keywords

BEVACIZUMAB; CETUXIMAB; CYCLOOXYGENASE 2; EPIDERMAL GROWTH FACTOR; EPIDERMAL GROWTH FACTOR RECEPTOR; EPIDERMAL GROWTH FACTOR RECEPTOR 2; EPIDERMAL GROWTH FACTOR RECEPTOR ANTIBODY; ERLOTINIB; FLUOROPYRIMIDINE DERIVATIVE; FLUOROURACIL; GEFITINIB; HETERODIMER; HOMODIMER; IRINOTECAN; LIGAND; MATUZUMAB; MITOGEN ACTIVATED PROTEIN KINASE; OXALIPLATIN; PANITUMUMAB; PERTUZUMAB; PLATELET DERIVED GROWTH FACTOR; PROTEIN TYROSINE KINASE; PROTEIN TYROSINE KINASE INHIBITOR; RAF PROTEIN; RAS PROTEIN; SOMATOMEDIN C RECEPTOR; SORAFENIB; UNCLASSIFIED DRUG; UNINDEXED DRUG; VASCULOTROPIN; VASCULOTROPIN RECEPTOR; VECTIBIX;

CANCER SURVIVAL; CELL CYCLE REGULATION; CLINICAL TRIAL; COLORECTAL CANCER; COMBINATION CHEMOTHERAPY; CYTOPLASM; DRUG MECHANISM; DRUG POTENTIATION; DRUG TARGETING; ENZYME ACTIVATION; GENE EXPRESSION; GENE MUTATION; GENE OVEREXPRESSION; HUMAN; IMMUNOHISTOCHEMISTRY; INTERNALIZATION; MONOTHERAPY; PREDICTION; PROTEIN DEGRADATION; PROTEIN FUNCTION; RECEPTOR INTRINSIC ACTIVITY; REVIEW; SIGNAL TRANSDUCTION; UBIQUITINATION; UNSPECIFIED SIDE EFFECT;

ANTINEOPLASTIC AGENTS; COLORECTAL NEOPLASMS; DRUG DELIVERY SYSTEMS; HUMANS; PREDICTIVE VALUE OF TESTS; RECEPTOR, EPIDERMAL GROWTH FACTOR;

EID: 34247562353     PISSN: 14737140     EISSN: 17448328     Source Type: Journal    
DOI: 10.1586/14737140.7.4.503     Document Type: Review

References (107)

1. Cohen S. Isolation of a mouse submaxillary gland protein accelerating incisor eruption and eyelid opening in the new-born animal. J. Biol. Chem. 237(6) 1555-1562 (1962).
2. Cohen S, Carpenter G, King L Jr. Epidermal growth factor-receptor-protein kinase interactions. Co-purification of receptor and epidermal growth factor-enhanced phosphorylation activity. J. Biol. Chem. 255(10), 4834-4842 (1980).
3. Salomon DS, Brandt R, Ciardiello F, Normanno N. Epidermal growth factor-related peptides and their receptors in human malignancies. Crit. Rev. Oncol. Hematol. 19(3), 183-232 (1995).
4. Barnes D, Sato G. Serum-free cell culture: a unifying approach. Cell 22(3), 649-655 (1980).
5. Kawamoto T, Sato JD, Le A et al. 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(5), 1337-1341 (1983).
6. Sato JD, Kawamoto T, Le AD et al. Biological effects in vitro of monoclonal antibodies to human epidermal growth factor receptors. Mol. Biol. Med. 1(5), 511-529 (1983).
7. Masui H, Kawamoto T, Sato JD et al. Growth inhibition of human tumor cells in athymic mice by anti-epidermal growth factor receptor monoclonal antibodies. Cancer Res. 44(3), 1002-1007 (1984).
8. Giaccone G, 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. J. Clin. Oncol. 22(5), 777-784 (2004).
9. Moore MJ, Goldstein D, Hamm J et al. Erlotinib plus gemcitabine compared to gemcitabine alone in patients with advanced pancreatic cancer. A Phase III trial of the National Cancer Institute of Canada Clinical Trials Group [NCIC-CTG]. J. Clin. Oncol. 23(Suppl. Pt 1), S16 (2005) (Abstract 1).
10. Normanno N, Bianco C, Strizzi L et al. The ErbB receptors and their ligands in cancer: an overview. Curr. Drug Targets 6(3), 243-257 (2005).
11. Saito T, Okada S, Ohshima K et al. Differential activation of epidermal growth factor (EGF) receptor downstream signaling pathways by betacellulin and EGF. Endocrinology 145(9), 4232-4243 (2004).
12. Tzahar E, Waterman H, Chen X et al. A hierarchical network of interreceptor interactions determines signal transduction by Neu differentiation factor/neuregulin and epidermal growth factor. Mol. Cell Biol. 16(10), 5276-5287 (1996).
13. Prenzel N, Fischer OM, Streit S, Hart S, Ullrich A. The epidermal growth factor receptor family as a central element for cellular signal transduction and diversification. Endocr. Relat. Cancer 8(1), 11-31 (2001).
14. Wu W, Graves LM, Gill GN, Parsons SJ, Samet JM. Src-dependent phosphorylation of the epidermal growth factor receptor on tyrosine 845 is required for zinc-induced Ras activation. J. Biol. Chem. 277(27), 24252-24257 (2002).
15. Schlessinger J, Lemmon MA. SH2 and PTB domains in tyrosine kinase signaling. Sci. STAKE 2003(191), RE12 (2003).
16. Pawson T, Olivier P, Rozakis-Adcock M, McGlade J, Henkemeyer M. Proteins with SH2 and SH3 domains couple receptor tyrosine kinases to intracellular signalling pathways. Philos. Trans. R. Soc. Lond. 340(1293), 279-285 (1993).
17. Shao H, Cheng HY, Cook RG, Tweardy DJ. Identification and characterization of signal transducer and activator of transcription 3 recruitment sites within the epidermal growth factor receptor. Cancer Res. 63(14), 3923-3930 (2003).
18. Buettner R, Mora LB, Jove R. Activated STAT signaling in human tumors provides novel molecular targets for therapeutic intervention. Clin. Cancer Res. 8(4), 945-954 (2002).
19. Lund KA, Lazar CS, Chen WS et al. Phosphorylation of the epidermal growth factor receptor at threonine 654 inhibits ligand-induced internalization and down-regulation. J. Biol. Chem. 265(33), 20517-20523 (1990).
20. Knowlden JM, Hutcheson IR, Barrow D, Gee JM, Nicholson RI. Insulin-like growth factor-I receptor signaling in tamoxifen-resistant breast cancer: a supporting role to the epidermal growth factor receptor. Endocrinology 146(11), 4609-4618 (2005).
21. Busse D, Doughty RS, Ramsey TT et al. Reversible G(1) arrest induced by inhibition of the epidermal growth factor receptor tyrosine kinase requires up-regulation of p27(KIP1) independent of MAPK activity. J. Biol. Chem. 275(10), 6987-6995 (2000).
22. Yardcn Y. The EGFR family and its ligands in human cancer: signalling mechanisms and therapeutic opportunities. Eur. J. Cancer 37(Suppl. 4), S3-S8 (2001).
23. Lenferink AE, Pinkas-Kramarski R, van de Poll ML et al. Differential endocytic routing of homo- and hetero-dimeric ErbB tyrosinc kinases confers signaling superiority to receptor heterodimers. EMBO J. 17(12), 3385-3397 (1998).
24. Venook A. Critical evaluation of current treatments in metastatic colorectal cancer. Oncologist 10(4), 250-261 (2005).
25. Tournigand C, Andre T, Achille E et al. FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J. Clin. Oncol. 22(2), 229-237 (2004).
26. Nicholson RI, Gee JM, Harper ME. EGFR and cancer prognosis. Eur. J. Cancer 37(Suppl. 4), S9-S15 (2001).
27. Zhang W, Park DJ, Lu B et al. Epidermal growth factor receptor gene polymorphisms predict pelvic recurrence in patients with rectal cancer treated with chemoradiation. Clin. Cancer Res. 11 (2 Pt 1), 600-605 (2005).
28. Kim JS, Kim JM, Li S et al. Epidermal growth factor receptor as a predictor of tumor downstaging in locally advanced rectal cancer patients treated with preoperative chemoradiotherapy. Int. J. Radiat. Oncol. Biol. Phys. 66(1), 195-200 (2006).
29. 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. USA 83(11), 3825-3829 (1986).
30. Cunningham D, Humbler Y, Siena S et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N. Engl. J. Med. 351(4), 337-345 (2004).
31. Venook A, Niedzweiecki D, Hollis D, et al. Phase III study of irinotecan/5FU/LV (FOLFIRI) or oxahplatin/5FU/LV (FOLFOX){±} cetuximab for patients (pts) with untreated metastatic adenocarcinoma of the colon or rectum (MCRC): CALGB 80203 preliminary results. Proc. Am. Soc. Clin. Oncol. 24, S148 (2006) (Abstract 3509).
32. Gibson TB, Ranganathan A, Grothey A. Randomized Phase III trial results of panitumumab, a fully human antiepidermal growth factor receptor monoclonal antibody, in metastatic colofectal cancer. Clin. Colorectal Cancer 6(1), 29-31 (2006).
33. Vanhoefer U, Tewes M, Rojo F et al. Phase I study of the humanized antiepidermal growth factor receptor monoclonal antibody EMD72000 in patients with advanced solid tumors that express the epidermal growth factor receptor. J. Clin. Oncol. 22(1), 175-184 (2004).
34. Arteaga CL, Johnson DH. Tyrosine kinase inhibitors-ZD1839 (Iressa®). Curr. Opin. Oncol. 13(6), 491-498 (2001).
35. Rothenberg ML, LaFleur B, Levy DE et al. Randomized Phase II trial of the clinical and biological effects of two dose levels of gefitinib in patients with recurrent colorectal adenocarcinoma. J. Clin. Oncol. 23(36), 9265-9274 (2005).
36. Townsley CA, Major P, Siu LL et al. Phase II study of erlotinib (OSI-774) in patients with metastatic colorectal cancer. Br. J. Cancer 94(8), 1136-1143 (2006).
37. Messersmith WA, Laheru DA, Senzer NN et al. Phase I trial of irinotecan, infusional 5-fluorouracil, and leucovorin (FOLFIRI) with erlotinib (OSI-774): early termination due to increased toxicities. Clin. Cancer Res. 10(19), 6522-6527 (2004).
38. Veronese ML, Sun W, Giantonio B et al. A Phase II trial of gefitinib with 5-fluorouracil, leucovorin, and irinotecan in patients with colorectal cancer. Br. J. Cancer 92(10), 1846-1849 (2005).
39. Kindler HL, Friberg G, Skoog L, Wade-Oliver K, Vokes EE. Phase I/II trial of gefitinib and oxaliplatin in patients with advanced colorectal cancer. Am. J. Oncol. 28(4), 340-344 (2005).
40. Knight LA, Di Nicolantonio F, Whitehouse P et al. The in vitro effect of gefitinib ('Iressa') alone and in combination with cytotoxic chemotherapy on human solid tumours. BMC Cancer 4, 83 (2004).
41. Dittmann K, Mayer C, Rodemann HP. Inhibition of radiation-induced EGFR nuclear import by C225 (Cetuximab) suppresses DNA-PK activity. Radiother. Oncol. 76(2), 157-161 (2005).
42. Huang S, Armstrong EA, Benavente S, Chinnaiyan P, Harari PM. Dual-agent molecular targeting of the epidermal growth factor receptor (EGFR): combining anti-EGFR antibody with tyrosine kinase inhibitor. Cancer Res. 64(15), 5355-5362 (2004).
43. Chung KY, Shia J, Kemeny NE et al. 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 (2005).
44. Atkins D, Reiffen KA. Tegtmeier CL et al. 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), 893-901 (2004).
45. Scartozzi M, Bearzi I, Berardi R et al. Epidermal growth factor receptor (EGFR) status in primary colorectal tumors does not correlate with EGFR expression in related metastatic sites: implications for treatment with EGFR-targeted monoclonal antibodies. J. Clin. Oncol. 22(23), 4772-4778 (2004).
46. Mutsaers AJ, Ebos JM, Lee C, et al. Circulating levels of ligand as a potential biomarker for optimal dosing of targeted antibody drugs to the epidermal growth factor receptor. Presented at: 18th EORTC-NCI-AACR Symposium (2006) (Abstract 217).
47. Zhang W, Gordon M, Press OA et al. Cyclin D1 and epidermal growth factor polymorphisms associated with survival in patients with advanced colorectal cancer treated with cetuximab. Pharmacogenet. Genomics 16(7), 475-483 (2006).
48. Viloria-Petit AM, Kerbel RS. Acquired resistance to EGFR inhibitors: mechanisms and prevention strategies. Int. J. Radiat. Oncol. Biol. Phys. 58(3), 914-926 (2004).
49. Mimori K, Yamashita K, Ohta M et al. Coexpression of matrix metalloproteinase-7 (MMP-7) and epidermal growth factor (EGF) receptor in colorectal cancer: an EGF receptor tyrosine kinase inhibitor is effective against MMP-7-expressing cancer cells. Clin. Cancer Res. 10(24), 8243-8249 (2004).
50. Prenzel N, Zwick E, Daub H et al. EGF receptor transactivation by G-protein-coupled receptors requires metalloproteinase cleavage of proHB-EGF. Nature 402(6764), 884-888 (1999).
51. Cunningham MP, Essapen S, Thomas H et al. Coexpression of the IGF-IR, EGFR and HER-2 is common in colorectal cancer patients. Int. J. Oncol. 28(2), 329-335 (2006).
52. Azuma M, Danenberg KD, Iqbal S et al. Epidermal growth factor receptor and epidermal growth factor receptor variant III gene expression in metastatic colorectal cancer. Clin. Colerectal Cancer 6(3), 214-218 (2006).
53. Li B, Yuan M, Kim IA et al. Mutant epidermal growth factor receptor displays increased signaling through the phosphatidylinositol-3 kinase/AKT pathway and promotes radioresistance in cells of astrocytic origin. Oncogene 23(26), 4594-4602 (2004).
54. 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(21), 2129-2139 (2004).
55. Barber TD, Vogelstein B, Kinzler KW, Velculescu VE. Somatic mutations of EGFR in colorectal cancers and glioblastomas. N. Engl. J. Med. 351(27), 2883 (2004).
56. Nagahara H, Mimori K, Ohta M et al. Somatic mutations of epidermal growth factor receptor in colorectal carcinoma. Clin. Cancer Res. 11(4), 1368-1371 (2005).
57. Lenz HJ, Van Cutsem E, Khambata-Ford S et al. Multicenter Phase II and translational study of cetuximab in metastatic colorectal carcinoma refractory to irinotecan, oxaliplatin, and fluoropyrimidines. J. Clin. Oncol. 24(30), 4914-4921 (2006).
58. Yang SH, Mechanic LE, Yang P et al. Mutations in the tyrosine kinase domain of the epidermal growth factor receptor in non-smaH cell lung cancer. Clin. Cancer Res. 11(6), 2106-2110 (2005).
59. Liu W, Innocenti F, Chen P et al. Interethnic difference in the allelic distribution of human epidermal growth factor receptor intron 1 polymorphism. Clin. Cancer Res. 9(3), 1009-1012 (2003).
60. Amador ML, Oppenheimer D, Perea S et al. An epidermal growth factor receptor intron 1 polymorphism mediates response to epidermal growth factor receptor inhibitors. Cancer Res. 64(24), 9139-9143 (2004).
61. Buerger H, Packeisen J, Boecker A et al. Allelic length of a CA dinucleotide repeat in the EGFR gene correlates with the frequency of amplifications of this sequence - first results of an inter-ethnic breast cancer study. J. Pathol. 203(1), 545-550 (2004).
62. Sauer T, Guren MG, Noren T, Dueland S. Demonstration of EGFR gene copy loss in colorectal carcinomas by fluorescence in situ hybridization (FISH): a surrogate marker for sensitivity to specific anti-EGFR therapy? Histopathology 47(6), 560-564 (2005).
63. Petrova D, Jankova I, Yosifova A et al. Tissue microarray analysis of EGFR gene amplification and gain in Bulgarian patients with colorectal cancer. Onkologie 29(5), 198-200 (2006).
64. Moroni M, Veronese S, Benvenuti S et al. Gene copy number for epidermal growth factor receptor (EGFR) and clinical response to antiEGFR treatment in colorectal cancer: a cohort study. Lancet Oncol. 6(5), 279-286 (2005).
65. Lievre A, Bachet JB, Le Corre D et al. KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer. Cancer Res. 66(8), 3992-3995 (2006).
66. Personeni N, Hendlisz A, Gallez J et al. Correlation between the response to cetuximab alone or in combination with irinotecan and the activated/phosphorylated epidermal growth factor receptor in metastatic colorectal cancer. Semin. Oncol. 32(6 Suppl. 9), 59-62 (2005).
67. Personeni NDS, De Hertogh J, Debiec-Rychter G et al. Response prediction to cetuximab-based therapy: the role of EGFR copy number by fluorescence in situ hybridization and downstream effectors gene mutations. Presented at: Gastrointestinal American Society of Clincal Oncology. FL, USA (2007) (Abstract 400).
68. Romagnani EM, Ghisletta V, Camponovo M et al. EGFR gene status, K-Ras mutation and PTEN expression predict cetuximab response in metastatic colorectal cancer (mCRC). Presented at: Gastrointestinal American Society of Clincal Oncology. FI, USA (2007) (Abstract 427).
69. Vallbohmer D, Zhang W, Gordon M et al. Molecular determinants of cetuximab efficacy. J. Clin. Oncol. 23(15), 3536-3544 (2005).
70. Van Schaeybroeck S, Karaiskou-McCaul A, Kelly D et al. Epidermal growth factor receptor activity determines response of colorectal cancer cells to gefitinib alone and in combination with chemotherapy. Clin. Cancer Res. 11(20), 7480-7489 (2005).
71. Cunningham MP, Essapen S, Thomas H et al. Compression, prognostic significance and predictive value of EGFR, EGFRvIII and phosphorylated EGFR in colorectal cancer. Int. J. Oncol. 27(2), 317-325 (2005).
72. Jones HE, Gee JM, Taylor KM et al. Development of strategies for the use of anti-growth factor treatments. Endocr. Relat. Cancer 12(Suppl. 1), S173-S182 (2005).
73. Kong A, Leboucher P, Leek R et al. Prognostic value of an activation state marker for epidermal growth factor receptor in tissue microarrays of head and neck cancer. Cancer Res. 66(5), 2834-2843 (2006).
74. Hakam A, Yeatman TJ, Lu L et al. Expression of insulin-like growth factor-1 receptor in human colorectal cancer. Hum. Pathol. 30(10), 1128-1133 (1999).
75. Adams TE, McKern NM, Ward CW. Signalling by the type 1 insulin-like growth factor receptor: interplay with the epidermal growth factor receptor. Growth Factors 22(2), 89-95 (2004).
76. Morelli MP, Cascone T, Troiani T et al. Anti-tumor activity of the combination of cetuximab, an anti-EGFR blocking monoclonal antibody and ZD6474, an inhibitor of VEGFR and EGFR tyrosine kinases. J. Cell Physiol. 208(2), 344-353 (2006).
77. Saltz LB, Lenz H, Hochster H et al. Randomized Phase II trial of cetuximab/bevacizumab/irinotecan (CBI) versus cetuximab/bevacizumab (CB) in irinotecanrefractory colorectal cancer. Proc. Am. Soc. Clin. Oncol. (2005) (Abstract 3508).
78. Adam L, Black G, Brown M et al. EGFR and PDGFR crosstalk may dictate the resistance to EGFR therapy in bladder cancer. Eur. J. Cancer (Suppl.) 64 (2006).
79. Sergina NV, Rausch M, Wang D et al. Escape from HER-family tyrosine kinase inhibitor therapy by the kinase-inactive HER3. Nature 445(7126), 437-441 (2007).
80. Dehm SM, Bonham K. SRC gene expression in human cancer: the role of transcriptional activation. Biochimie Biologie Cellulaire 82(2), 263-274 (2004).
81. Bos JL. Ras oncogenes in human cancer: a review. Cancer Res. 49(17), 4682-4689 (1989).
82. Xiong HQ, Rosenberg A, LoBuglio A et al. Cetuximab, a monoclonal antibody targeting the epidermal growth factor receptor, in combination with gemcitabine for advanced pancreatic cancer: a multicenter Phase II trial. J. Clin. Oncol. 22(13), 2610-2616 (2004).
83. Baumann M, Krause M. Targeting the epidermal growth factor receptor in radiotherapy: radiobiological mechanisms, preclinical and clinical results. Radiother. Oncol. 72(3), 257-266 (2004).
84. Toulany M, Dittmann K, Kruger M, Baumann M, Rodemann HP. Radioresistance of K-Ras mutated human tumor cells is mediated through EGFR-dependent activation of PI3K-AKT pathway. Radiother. Oncol. 76(2), 143-150 (2005).
85. Nagasaka T, Sasamoto H, Notohara K et al. Colorectal cancer with mutation in BRAF, KRAS, and wild-type with respect to both oncogenes showing different patterns of DNA methylation. J. Clin. Oncol. 22(22), 4584-4594 (2004).
86. Cohen SJ, Cohen RB, Meropol NJ. Targeting signal transduction pathways in colorectal cancer - more than skin deep. J. Clin. Oncol. 23(23), 5374-5385 (2005).
87. Hoshino R, Chatani Y, Yamori T et al. Constitutive activation of the 41-/43-κDa mitogen-activated protein kinase signaling pathway in human tumors. Oncogene 18(3), 813-822 (1999).
88. Philp AJ, Campbell IG, Leer C et al. The phosphatidylinositol 3′-kinasc p85α gene is an oncogene in human ovarian and colon tumors. Cancer Res. 61(20), 7426-7429 (2001).
89. Samuels Y, Velculescu VE. Oncogenic mutations of PIK3CA in human cancers. Cell cycle 3(10), 1221-1224 (2004).
90. Cunningham MP, Thomas H, Fan Z, Modjtahedi H. Responses of human colorectal tumor cells to treatment with the anti-epidermal growth factor receptor monoclonal antibody ICR62 used alone and in combination with the EGFR tyrosine kinase inhibitor gefitinib. Cancer Res. 66(15), 7708-7715 (2006).
91. Ogino S, Meyerhardt JA, Cantor M et al. Molecular alterations in tumors and response to combination chemotherapy with gefitinib for advanced colorectal cancer. Clin. Cancer Res. 11(18), 6650-6656 (2005).
92. Salara RT, Rojo J, Jimenez E et al. Dose-dependent inhibition of the EGFR and signalling pathways with the anti-EGFR monoclonal antibody (MAb) EMD 72000 administered every three weeks (q3w). A Phase I pharmacokinetic/pharmacodynamic (PK/PD) study to define the optimal biological dose (OBD). Proc. Am. Soc. Clin. Oncol. (2004) (Abstract 2002).
93. Cappuzzo F, Magrini E, Ceresoli GL et al. Akt phosphorylation and gefitinib efficacy in patients with advanced non-small-cell lung cancer. J. Natl Cancer Inst. 96(15), 1133-1141 (2004).
94. Bianco R, Shin I, Ritter CA et al. Loss of PTEN/MMAC1/TEP in EGF receptor-expressing tumor cells counteracts the antitumor action of EGFR tyrosine kinase inhibitors. Oncogene 22(18), 2812-2822 (2003).
95. Goel A, Arnold CN, Niedzwiecki D et al. Frequent inactivation of PTEN by promoter hypermethylation in microsatellite instability-high sporadic colorectal cancers. Cancer Res. 64(9), 3014-3021 (2004).
96. Zhou XP, Loukola A, Salovaara R et al. PTEN mutational spectra, expression levels, and subcellular localization in microsatellite stable and unstable colorectal cancers. Am. J. Pathol. 161(2), 439-447 (2002).
97. Corvinus FM, Orth C, Moriggl R et al. Persistent STAT3 activation in colon cancer is associated with enhanced cell proliferation and tumor growth. Neoplasia 7(6), 545-555 (2005).
98. Lin Q, Lai R, Chirieac LR et al. Constitutive activation of JAK3/ STAT3 in colon carcinoma tumors and cell lines: inhibition of JAK3/STAT3 signaling induces apoptosis and cell cycle arrest of colon carcinoma cells. Am. J. Pathol. 167(4), 969-980 (2005).
99. Liu D, Aguirre Ghiso J, Estrada Y, Ossowski L. EGFR is a transducer of the urokinase receptor initiated signal that is required for in vivo growth of a human carcinoma. Cancer Cell 1(5), 445-457 (2002).
100. Choong PF, Nadesapillai AP. Urokinase plasminogen activator system: a multifunctional role in tumor progression and metastasis. Clin. Orthop. Relat. Res. (415 Suppl.), S46-S58 (2003).
101. Yauch RL, Januario T, Eberhard DA et al. Epithelial versus mesenchymal phenotype determines in vitro sensitivity and predicts clinical activity of erlotinib in lung cancer patients. Clin. Cancer Res. 11(24 Pt 1), 8686-8698 (2005).
102. Torrance CJ, Jackson PE, Montgomery E et al. Combinatorial chemoprevention of intestinal neoplasia. Nat. Med. 6(9), 1024-1028 (2000).
103. Jimeno A, Rubio-Viqueira B, Amador ML et al. Epidermal growth factor receptor dynamics influences response to epidermal growth factor receptor targeted agents. Cancer Res. 65(8), 3003-3010 (2005).
104. Perez-Soler R, Saltz L. Cutaneous adverse effects with HER1/ EGFR-targeted agents: is there a silver lining? J. Clin. Oncol. 23(22), 5235-5246 (2005).
105. Levkowitz G, Waterman H, Ettenberg SA et al. Ubiquitin ligase activity and tyrosine phosphorylation underlie suppression of growth factor signaling by c-Cbl/Sli-1. Mol. Cell 4(6), 1029-1040 (1999).
106. Levkowitz G, Waterman H, Zamir E et al. c-Cbl/Sli-1 regulates endocytic sorting and ubiquitination of the epidermal growth factor receptor. Genes Dev. 12(23), 3663-3674 (1998).
107. Burgess AW, Cho HS, Eigenbrot C et al. An open and shut case? Recent insights into the activation of EGFR/ErbB receptors. Mol. Cell 12(3), 541-552 (2003).