Surrogate predictive biomarkers for response to anti-EGFR agents: State of the art and challenges

International Journal of Biological Markers

Volumn 22, Issue 1 SUPPL. 4, 2007, Pages

  Cappuzzo, Federico ^a   Toschi, L ^a   Finocchiaro, G ^a   Ligorio, C ^a   Santoro, A ^a  

^a HUMANITAS CLINICAL AND RESEARCH CENTER   (Italy)

Author keywords

EGFR; Erlotinib; Gefitinib; NSCLC; Tyrosine kinase inhibitors

Indexed keywords

6 (4 HYDROXYPHENYL) 4 (ALPHA METHYLBENZYLAMINO) 7H PYRROLO[2,3 D]PYRIMIDINE; 6 [4 (4 ETHYL 1 PIPERAZINYLMETHYL)PHENYL] 4 (ALPHA METHYLBENZYLAMINO) 7H PYRROLO[2,3 D]PYRIMIDINE; ABX EFG; ANTINEOPLASTIC AGENT; CANERTINIB; CETUXIMAB; CISPLATIN; DNA; EDM 72000; EPIDERMAL GROWTH FACTOR RECEPTOR 2; EPIDERMAL GROWTH FACTOR RECEPTOR KINASE; EPIDERMAL GROWTH FACTOR RECEPTOR KINASE 3; EPIDERMAL GROWTH FACTOR RECEPTOR KINASE INHIBITOR; ERLOTINIB; GEFITINIB; HKI 272; HKI 357; K RAS PROTEIN; LAPATINIB; MATUZUMAB; MDX 214; MESSENGER RNA; MONOCLONAL ANTIBODY; NAVELBINE; PANITUMUMAB; PELITINIB; PERTUZUMAB; PHOSPHATIDYLINOSITOL 3 KINASE; PLACEBO; PROTEIN TYROSINE KINASE INHIBITOR; TUMOR MARKER; UNCLASSIFIED DRUG; VANDETANIB;

ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER INHIBITION; CANCER RESISTANCE; CANCER SURVIVAL; CARCINOGENESIS; CLINICAL TRIAL; COLORECTAL CANCER; COMBINATION CHEMOTHERAPY; DIARRHEA; DNA SEQUENCE; DRUG EFFICACY; DRUG ERUPTION; DRUG RECEPTOR BINDING; DRUG RESPONSE; DRUG SAFETY; DRUG SENSITIVITY; DRUG TOLERABILITY; DRUG TREATMENT FAILURE; FLUORESCENCE IN SITU HYBRIDIZATION; GENE EXPRESSION; GENE MUTATION; HEAD AND NECK CANCER; HUMAN; IMMUNOHISTOCHEMISTRY; LUNG ADENOCARCINOMA; LUNG ALVEOLUS CELL CARCINOMA; LUNG NON SMALL CELL CANCER; MONOTHERAPY; OVERALL SURVIVAL; QUANTITATIVE ANALYSIS; REAL TIME POLYMERASE CHAIN REACTION; SKIN TOXICITY;

EID: 34248362268     PISSN: 03936155     EISSN: None     Source Type: Journal    
DOI: 10.5301/jbm.2008.5699     Document Type: Article

References (134)

1. Shibuya K, Mathers CD, Boschi-Pinto C, Lopez AD, Murray CJ. Global and regional estimates of cancer mortality and incidence by site: II. Results for the global burden of disease 2000. BMC Cancer 2002; 2: 37.
2. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2006. CA Cancer J Clin 2006; 56: 106-30.
3. Schiller JH, Harrington D, Belani CP, et al. Eastern Cooperative Oncology Group. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med 2002; 346: 92-8.
4. Kelly K, Crowley J, Bunn PA Jr, et al. Randomized phase III trial of paclitaxel plus carboplatin versus vinorelbine plus cisplatin in the treatment of patients with advanced non-small-cell lung cancer: a Southwest oncology Group trial. J Clin Oncol 2001; 19: 3210-8.
5. Hanna N, Shepherd FA, Fossella FV, et al. Randomized, multinational, phase III study of docetaxel plus platinum combinations versus vinorelbine plus cisplatin for advanced non-small-cell lung cancer: the TAX 326 study group. J Clin Oncol 2004; 21: 3016-24.
6. Gridelli C, Perrone F, Gallo C, et al. Chemotherapy for elderly patients with advanced non-small-cell lung cancer: the Multicenter Italian Lung Cancer in the Elderly Study (MILES) phase III randomized trial. J Natl Cancer Inst 2003; 95: 362-72.
7. Salomon DS, Brandt R, Ciardiello F, et al. Epidermal growth factor-related peptides and their receptors in human malignancies. Crit Rev Oncol Hematol 1995; 19: 183-232.
8. Arteaga C. Overview of epidermal growth factor receptor biology and its role as a therapeutic target in human neoplasia. Semin Oncol 2002; 29: 3-9.
9. Woodburn JR. The epidermal growth factor receptor and its inhibition in cancer therapy. Pharmacol Ther 1999; 82: 241-50.
10. Mendelsohn J, Baselga J. The EGF receptor family as targets for cancer therapy. Oncogene 2000; 19: 6550-65.
11. Shepherd FA, Rodrigues Pereira J, Ciuleanu T, et al. National Cancer Institute of Canada Clinical Trials Group. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med 2005; 353: 123-32.
12. Sandler AB, Gray R, Perry MC, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small cell lung cancer. N Engl J Med 2006; 355: 2542-50.
13. Bunn PA Jr, Franklin W. Epidermal growth factor receptor expression, signal pathway, and inhibitors in non-small cell lung cancer. Semin Oncol 2002; 29 (suppl 14): 38-44.
14. Natale RB. Biologically targeted treatment of non-small-cell lung cancer: focus on epidermal growth factor receptor. Clin Lung Cancer 2003; 5 (suppl 1): S11-7.
15. 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 2003; 21: 2237-46.
16. 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. J Am Med Assoc 2003; 290: 2149-58.
17. Perez-Soler R, Chachoua A, Huberman M, et al. Final results of a phase II study of erlotinib (Tarceva) monotherapy in patients with advanced nonsmall cell lung cancer following failure of platinum based chemotherapy. Lung Cancer 2003; 41 (suppl 2): S246.
18. Ciaccone 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 2004; 22: 777-84.
19. 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. J Clin Oncol 2004; 22: 785-94.
20. Gatzemeier U, Pluzanska A, Szczesna A, et al. 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). Proc Am Soc Clin Oncol 2004; 22: 617s (abstr 7010).
21. Herbst RS, Prager D, Hermann R, et al. TRIBUTE - A phase III trial of erlotinib hydrochloride (OSI-774) combined with carboplatin and paclitaxel chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol 2005; 23: 5892-9.
22. Tracy S, Mukohara T, Hansen M, Meyerson M, Johnson BE, Janne PA. Gefitinib induces apoptosis in the EGFRL858R non-small-cell lung cancer cell line H3255. Cancer Res 2004; 64: 7241-4.
23. Solit DB, She Y, Lobo J, et al. Pulsatile administration of the epidermal growth factor receptor inhibitor gefitinib is significantly more effective than continuous dosing for sensitizing tumors to paclitaxel. Clin Cancer Res 2005; 11: 1983-9.
24. Gandara D, Narayan S, Lara PN Jr, et al. Integration of novel therapeutics into combined modality therapy of locally advanced non-small cell lung cancer. Clin Cancer Res 2005; 11: 5057s-62s.
25. Thatcher N, Chang A, Parikh P, et al. Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: results from a randomised, placebo-controlled, multicentre study (Iressa Survival Evaluation in Lung Cancer). Lancet 2005; 366: 1527-37.
26. Cunningham D, Humblet Y, Siena S, et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 2004; 351: 337-45.
27. Bonner J, Harari P, Giralt J, et al. Radiotherapy plus cetuximab for squamous cell carcinoma of the head and neck. N Engl J Med 2006; 354: 567-78.
28. Goldstein N, Prewett M, Zuklys K, et al. Biological efficacy of a chimeric antibody to the epidermal growth factor receptor in a human tumor xenograft model. Clin Cancer Res 1995; 1: 1311-8.
29. Waksal H. Role of an anti-epidermal growth factor receptor in treating cancer. Cancer Metastasis Rev 1999; 18: 427-36.
30. Yarden Y, Ullrich A. Growth factor receptor tyrosine kinases. Annu Rev Biochem 1988; 57: 443-78.
31. Hanna N, Lilenbaum R, Ansari R, et al. Phase II trial of cetuximab in patients with previously treated non-small-cell lung cancer. J Clin Oncol 2006; 24: 5253-8.
32. Kim ES, Mauer AM, Tran HT, et al. A phase II study of cetuximab, an epidermal growth factor receptor (EGFR) blocking antibody, in combination with docetaxel in chemotherapy refractory/resistant patients with advanced non-small cell lung cancer: Final report. Proc Am Soc Clin Oncol 2003; 22: 642s (abstr 2581).
33. Rosell R, Daniel C, Ramlau R, et al. Randomized phase II study of cetuximab in combination with cisplatin (C) and vinorelbine (V) vs. CV alone in the first-line treatment of patients (pts) with epidermal growth factor receptor (EGFR)-expressing advanced non-small-cell lung cancer (NSCLC). Proc Am Soc Clin Oncol 2004; 23: 618s (abstr 7012).
34. Mukohara T, Engelman JA, Hanna NH, et al. Differential effects of gefitinib and cetuximab on non-small-cell lung cancers bearing epidermal growth factor receptor mutations. J Natl Cancer Inst 2005; 97: 1185-94.
35. Miller VA, Kris MG, Shah N, et al. Bronchioloalveolar pathologic subtype and smoking history predict sensitivity to gefitinib in advanced non-small-cell lung cancer. J Clin Oncol 2004; 22: 1103-9.
36. Lee DH, Han JY, Lee HG, et al. Gefitinib as a first-line therapy of advanced or metastatic adenocarcinoma of the lung in never-smokers. Clin Cancer Res 2005; 11: 3032-7.
37. Ceresoli GL, Cappuzzo F, Gregorc V, Bartolini S, Crino L, Villa E. Gefitinib in patients with brain metastases from non-small-cell lung cancer: a prospective trial. Ann Oncol 2004; 15: 1042-7.
38. Cappuzzo F, Ardizzoni A, Soto-Parra H, et al. Epidermal growth factor receptor targeted therapy by ZD 1839 (Iressa) in patients with brain metastases from non-small cell lung cancer (NSCLC). Lung Cancer 2003; 41: 227-31.
39. Cappuzzo F, Calandri C, Bartolini S, Crino L. ZD 1839 in patients with brain metastases from non-small-cell lung cancer (NSCLC): report of four cases. Br J Cancer 2003; 89: 246-7.
40. Clark GM, Zborowski D, Santabgrbara P, et al. Smoking history and epidermal growth factor receptor expression as predictors of survival benefit from erlotinib for patients with non-small-cell lung cancer in the National Cancer Institute of Canada Clinical Trials Group study BR.21. Clin Lung Cancer 2006; 7: 389-94.
41. Sanchez-Cespedes M, Ahrendt SA, Piantadosi S, et al. Chromosomal alterations in lung adenocarcinoma from smokers and nonsmokers. Cancer Res 2001; 61: 1309-13.
42. Ahrendt SA, Decker PA, Alawi EA, et al. Cigarette smoking is strongly associated with mutation of the K-ras gene in patients with primary adenocarcinoma of the lung. Cancer 2001; 92: 1525-30.
43. Slebos RJ, Hruban RH, Dalesio O, et al. Relationship between K-ras oncogene activation and smoking in adenocarcinoma of the human lung. J Natl Cancer Inst 1991; 83: 1024-7.
44. Pao W, Wang TY, Riely GJ, et al. KRAS mutations and primary resistance of lung adenocarcinomas to gefitinib or erlotinib. PLoS Med 2005; 2: e17.
45. 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 2004 ; 350: 2129-39.
46. Paez JG, Jänne PA, Lee JC, et al. EGFR mutations in lung cancer: Correlation with clinical response to gefitinib therapy. Science 2004; 304: 1497-500.
47. Cappuzzo F, Hirsch FR, Rossi E, et al. Epidermal growth factor receptor gene and protein and gefitinib sensitivity in non-small cell lung cancer. J Natl Cancer Inst 2005; 97: 643-55.
48. Pao W, Miller V, Zakowski M, et al. EGF receptor gene mutations are common in lung cancer from «never-smoker» and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc Natl Acad Sci U S A 2004; 101: 13306-11.
49. Takano T, Ohe Y, Sakamoto H, et al. Epidermal growth factor receptor gene mutations and increased copy numbers predict gefitinib sensitivity in patients with recurrent non-small-cell lung cancer. J Clin Oncol 2005; 23: 6829-37.
50. Shigematsu H, Lin L, Takahashi T, et al. Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancers. J Natl Cancer Inst 2005; 97: 339-46.
51. Pham D, Kris MG, Riely GJ, et al. Use of cigarette-smoking history to estimate the likelihood of mutations in epidermal growth factor receptor gene exons 19 and 21 in lung adenocarcinomas. J Clin Oncol 2006; 24: 1700-4.
52. Mohamed MK, Ramalingam S, Lin Y, Gooding W, Belani CP. Skin rash and good performance status predict improved survival with gefitinib in patients with advanced non-small cell lung cancer. Ann Oncol 2005; 16: 780-5.
53. Perez-Soler R. Can rash associated with HER1/EGFR inhibition be used as a marker of treatment outcome? Oncology 2003; 17: 23-8.
54. Saltz L, Kies M, Abbruzzese JL, et al. The presence and intensity of the cetuximab-incluced acne-like rash predicts increased survival in studies across multiple malignancies. Proc Am Soc Clin Oncol 2003; 22: 817.
55. 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 2004; 64: 9139-43.
56. Bailey LR, Kris M, Wolf M, et al. Tumor EGFR membrane staining is not clinically relevant for predicting response in patients receiving gefitinib ('Iressa', ZD1839) monotherapy for pretreated advanced non-small-cell lung cancer: IDEAL 1 and 2. Proc Am Assoc Cancer Res 2003; 44: 1362, LB-170.
57. Cappuzzo F, Gregorc V, Rossi E, et al. Gefitinib in pretreated non-small-cell lung cancer (NSCLC): analysis of efficacy and correlation with HER2 and epidermal growth factor receptor expression in locally advanced or metastatic NSCLC. J Clin Oncol 2003; 21: 2658-63.
58. Miller VA, Zakowski M, Riely GJ, et al. EGFR mutation and copy number, EGFR protein expression and KRAS mutation as predictors of outcome with erlotinib in bronchioloalveolar cell carcinoma: results of a prospective phase II trial. Proc Am Soc Clin Oncol 2006; 24 (18s): 7003.
59. Villaflor VM, Buckingham L, Gale M, et al. EGFR mutations (muts), IHC and FISH status, and chromosome 7 gene copy number combined with pAkt expression as potential predictors of survival in non-small cell lung cancer (NSCLC) patients (pts) treated with gefitinib (GEF). Proc Am Soc Clin Oncol 2006; 24 (18s): 7182.
60. Tsao MS, Sakurada A, Cutz JC, et al. Erlotinib in lung cancer - molecular and clinical predictors of outcome. N Engl J Med 2005; 353: 133-44.
61. Hirsch FR, Varella-Garcia M, Bunn PA, et al. Molecular predictors of outcome with gefitinib in a phase III placebo-controlled study in advanced non-small-cell lung cancer. J Clin Oncol 2006; 24: 5034-42.
62. Greulich H, Chen TH, Feng W, et al. Oncogenic transformation by inhibitor-sensitive and -resistant EGFR mutants. PloS Med 2005; 2: e313.
63. Marchetti A, Felicioni L, Buttitta F. Assessing EGFR mutations. N Engl J Med 2006; 354: 526-8.
64. Bell DW, Gore I, Okimoto RA, et al. Inherited susceptibility to lung cancer may be associated with the T790M drug resistance mutation in EGFR. Nat Genet 2005; 37: 1315-6.
65. Kobayashi S, Boggon TJ, Dayaram T, et al. EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N Engl J Med 2005; 352: 786-92.
66. Han SW, Kim TY, Hwang PG, et al. Predictive and prognostic impact of epidermal growth factor receptor mutation in nonsmall-cell lung cancer patients treated with gefitinib. J Clin Oncol 2005; 23: 2493-501.
67. Kim KS, Jeong JY, Kim YC, et al. Predictors of the response to gefitinib in refractory non-small cell lung cancer. Clin Cancer Res 2005; 11: 2244-51.
68. Cortes-Funes H, Gomez C, Rosell R, et al. Epidermal growth factor receptor activating mutations in Spanish gefitinib-treated non-small cell lung cancer patients. Ann Oncol 2005; 16: 1081-6.
69. Villaflor VM, Buckingham L, Gale M, et al. EGFR mutations and pAKT expression as potential predictors of gefitinib efficacy in non-small cell lung cancer (NSCLC) patients (pts). Proc Am Soc Clin Oncol 2005; 23 (16s): 7077.
70. Chou TY, Chiu CH, Li LH, et al. Mutation in the tyrosine kinase domain of epidermal growth factor receptor is a predictive and prognostic factor for gefitinib treatment in patients with non-small cell lung cancer. Clin Cancer Res 2005; 11: 3750-7.
71. Taron M, Ichinose Y, Rosell R, et al. Activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor are associated with improved survival in gefitinib-treated chemorefractory lung adenocarcinomas. Clin Cancer Res 2005; 11: 5878-85.
72. Mu XL, Li LY, Zhang XT, et al. Gefitinib-sensitive mutations of the epidermal growth factor receptor tyrosine kinase domain in Chinese patients with non-small cell lung cancer. Clin Cancer Res 2005; 11: 4289-94.
73. Zhang XT, Li LY, Mu XL, et al. The EGFR mutation and its correlation with response of gefitinib in previously treated Chinese patients with advanced non-small-cell lung cancer. Ann Oncol 2005; 16: 1334-42.
74. Mitsudomi T, Kosaka T, Endoh H, et al. Mutations of the epidermal growth factor receptor gene predict prolonged survival after gefitinib treatment in patients with non-small-cell lung cancer with postoperative recurrence. J Clin Oncol 2005; 23: 2513-20.
75. Paz-Ares L, Sanchez JM, Garcfa-Velasco A, et al. A prospective phase II trial of erlotinib in advanced non-small cell lung cancer (NSCLC) patients (p) with mutations in the tyrosine kinase (TK) domain of the epidermal growth factor receptor (EGFR). Proc Am Soc Clin Oncol 2006; 24 (18s): 7020.
76. Inoue A, Suzuki T, Fukuhara T, et al. Prospective phase II study of gefitinib for chemotherapy-naive patients with advanced non-small-cell lung cancer with epidermal growth factor receptor gene mutations. J Clin Oncol 2006; 24: 3340-6.
77. Okamoto I, Kashii T, Urata Y, et al. EGFR mutation-based phase II multicenter trial of gefitinib in advanced non-small cell lung cancer (NSCLC) patients (pts): Results of West Japan Thoracic Oncology Group trial (WJTOG0403). Proc Am Soc Clin Oncol 2006; 24 (18s): 7073.
78. Sutani A, Nagai Y, Udagawa K, et al. Phase II study of gefitinib for non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) gene mutations detected by PNA-LNA PCR clamp. Proc Am Soc Clin Oncol 2006; 24: (18s): 7076.
79. Sunaga N, Yanagitani N, Kaira K, et al. Phase II study of the efficacy of gefitinib in patients with non-small cell lung cancer with the EGFR mutations. Proc Am Soc Clin Oncol 2006; 24 (18s): 7183.
80. Asahina H, Yamazaki K, Kinoshita I, et al. phase II study of gefitinib as a first-line therapy for advanced non-small cell lung cancers with epidermal growth factor receptor (EGFR) gene mutations. Proc Am Soc Clin Oncol 2006; 24 (18s): 13014.
81. Bell DW, Lynch TJ, Haserlat SM, et al. Epidermal growth factor receptor mutations and gene amplification in non-small-cell lung cancer: molecular analysis of the IDEAL/INTACT gefitinib trials. J Clin Oncol 2005; 23: 8081-92.
82. Eberhard DA, Johnson BE, Amler LC, et al. 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 2005; 23: 5900-9.
83. Gatzemeier U, Heller A, Foernzler D, et al. Exploratory analyses EGFR, kRAS mutations and other molecular markers in tumors of NSCLC patients (pts) treated with chemotherapy +/- erlotinib (TALENT). Proc Am Soc Clin Oncol 2005; 23 (16s): 7028.
84. Riely GJ, Pao W, Pham D, et al. Clinical course of patients with non-small cell lung cancer and epidermal growth factor receptor exon 19 and exon 21 mutations treated with gefitinib or erlotinib. Clin Cancer Res 2006; 12: 839-44.
85. Jackman DM, Yeap BY, Sequist LV, et al. Exon 19 deletion mutations of epidermal growth factor receptor are associated with prolonged survival in non-small cell lung cancer patients treated with gefitinib or erlotinib. Clin Cancer Res 2006; 12: 3908-14.
86. Hirsch FR, Franklin WA, McCoy J, et al. Predicting clinical benefit from EGFR TKIs: Not all EGFR mutations are equal. Proc Am Soc Clin Oncol 2006; 24 (18s): 7072.
87. Hirsch FR, Varella-Garcia M, McCoy J, et al. 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 2005; 23: 6838-45.
88. Dziadziuszko R, Witta SE, Cappuzzo F, et al. Epidermal growth factor receptor messenger RNA expression, gene dosage, and gefitinib sensitivity in non-small cell lung cancer. Clin Cancer Res 2006; 12: 3078-84.
89. Lenferink AE, Pinkas-Kramarski R, van de Poll ML, et al. Differential endocytic routing of homo- and hetero-dimeric ErbB tyrosine kinases confers signaling superiority to receptor heterodimers. EMBO J 1998; 17: 3385-97.
90. Moasser MM, Basso A, Averbuch SD, et al. The tyrosine kinase inhibitor ZD1839 ("Iressa") inhibits HER2-driven signaling and suppresses the growth of HER2-overexpressing tumor cells. Cancer Res 2001; 61: 7184-8.
91. Moulder SL, Yakes FM, Muthuswamy SK, et al. Epidermal growth factor receptor (HERI) tyrosine kinase inhibitor ZD1839 (Iressa) inhibits HER2/ neu (erbB2)-overexpressing breast cancer cells in vitro and in vivo. Cancer Res 2001; 61: 8887-95.
92. Normanno N, Campiglio M, De LA, et al. Cooperative inhibitory effect of ZD1839 (Iressa) in combination with trastuzumab (Herceptin) on human breast cancer cell growth. Ann Oncol 2002; 13: 65-72.
93. Anido J, Matar P, Albanell J, et al. ZD1 839, a specific epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, induces the formation of inactive EGFR/HER2 and EGFR/HER3 heterodimers and prevents heregulin signaling in HER2-overexpressing breast cancer cells. Clin Cancer Res 2003; 9: 1274-83.
94. Hirata A, Hosoi F, Miyagawa M, et al. HER2 overexpression increases sensitivity to gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, through inhibition of HER2/HER3 heterodimer formation in lung cancer cells. Cancer Res 2005; 65: 4253-60.
95. Cappuzzo F, Varella-Garcia M, Shigematsu H, et al. Increased HER2 gene copy number is associated with response to gefitinib therapy in epidermal growth factor receptor-positive non-small-cell lung cancer patients. J Clin Oncol 2005; 23: 5007-18.
96. Guy PM, Platko JV, Cantley LC, Cerione RA, Carraway KL 3rd. Insect cell-expressed p180erbB3 possesses an impaired tyrosine kinase activity. Proc Natl Acad Sci USA 1994; 91: 8132-6.
97. Landgraf R, Eisenberg D. Heregulin reverses the oligomerization of HER3. Biochemistry 2000; 39: 8503-11.
98. Cho HS, Leahy DJ. Structure of the extracellular region of HER3 reveals an interdomain tether. Science 2002; 297: 1330-3.
99. Sliwkowski MX, Schaefer G, Akita RW, et al. Coexpression of erbB2 and erbB3 proteins reconstitutes a high affinity receptor for heregulin. J Biol Chem 1994; 269: 14661-5.
100. Naidu R, Yadav M, Nair S, Kutty MK. Expression of c-erbB3 protein in primary breast carcinomas. Br J Cancer 1998; 78: 1385-90.
101. Krahn G, Leiter U, Kaskel P, et al. Coexpression patterns of EGFR, HER2, HER3 and HER4 in non-melanoma skin cancer. Eur J Cancer 2001; 37: 251-9.
102. Chen X, Yeung TK, Wang Z. Enhanced drug resistance in cells coexpressing ErbB2 with EGF receptor or ErbB3. Biochem Biophys Res Commun 2000; 277: 757-63.
103. 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 2004; 6: 1133-41.
104. Fedi P, Pierce JH, di Fiore PP, Kraus MH. Efficient coupling with phosphatidylinositol 3-kinase, but not phospholipase C gamma or GTPase-activating protein, distinguishes ErbB-3 signaling from that of other ErbB/EGFR family members. Mol Cell Biol 1994; 14: 492-500.
105. Engelman JA, Janne PA, Mermel C, et al. ErbB-3 mediates phosphoinositide 3-kinase activity in gefitinib-sensitive non-small cell lung cancer cell lines. Proc Natl Acad Sci USA 2005; 102: 3788-93.
106. Cappuzzo F, Toschi L, Domenichini I, et al. HER3 genomic gain and sensitivity to gefitinib in advanced non-small-cell lung cancer patients. Br J Cancer 2005; 93: 1334-40.
107. Han SW, Hwang PG, Chung DH, et al. Epidermal growth factor receptor (EGFR) downstream molecules as response predictive markers for gefitinib (Iressa, ZD1839) in chemotherapy-resistant non-small cell lung cancer. Int J Cancer 2005; 113: 109-15.
108. Sordella R, Bell DW, Haber DA, Settleman J. Gefitinib-sensitizing EGFR mutations in lung cancer activate anti-apoptotic pathways. Science 2004; 305: 1163-7.
109. Ono M, Hirata A, Kometani T, et al. Sensitivity to gefitinib (Iressa, ZD1839) in non-small cell lung cancer cell lines correlates with dependence on the epidermal growth factor (EGF) receptor/extracellular signal-regulated kinase 1/2 and EGF receptor/Akt pathway for proliferation. Mol Cancer Ther 2004; 3: 465-72.
110. 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 2003; 22: 2812-22.
111. Janmaat ML, Kruyt FA, Rodriguez JA, Giaccone G. Response to epidermal growth factor receptor inhibitors in non-small cell lung cancer cells: limited anti proliferative effects and absence of apoptosis associated with persistent activity of extracellular signal-regulated kinase or Akt kinase pathways. Clin Cancer Res 2003; 9: 2316-26.
112. Wang SE, Narasanna A, Perez-Torres M, et al. HER2 kinase domain mutation results in constitutive phosphorylation and activation of HER2 and EGFR and resistance to EGFR tyrosine kinase inhibitors. Cancer Cell 2006; 10: 25-38.
113. Cappuzzo F, Toschi L, Trisolini R, et al. Clinical and biological effects of gefitinib in EGFR FISH positive/phosphor-Akt positive or never smoker non-small cell lung cancer (NSCLC): Preliminary results of te ONCOBELL trial. Proc Am Soc Clin Oncol 2006; 24 (18s): 7023.
114. Marchetti A, Martella C, Felicioni L, et al. EGFR mutations in non-small-cell lung cancer: analysis of a large series of cases and development of a rapid and sensitive method for diagnostic screening with potential implications on pharmacologic treatment. J Clin Oncol 2005; 23: 857-65.
115. Rodenhuis S, Slebos RJC, Boot AJM, et al. Incidence and possible clinical significance of K-ras oncogene activation in adenocarcinoma of the human lung. Cancer Res 1988; 48: 5738-41.
116. Suzuki Y, Orita M, Shiraishi M, et al. Detection of ras gene mutations in human lung cancers by single-strand conformation polymorphism analysis of polymerase chain reaction products. Oncogene 1990; 5: 1037-43.
117. Nelson HH, Christiani DC, Mark EJ, et al. Implications and prognostic value of K-ras mutation for early-stage lung cancer in women. J Natl Cancer Inst 1999; 91: 2032-8.
118. Broermann P, Junker K, Brandt BH, et al. Trimodality treatment in stage III nonsmall cell lung carcinoma: Prognostic impact of K-ras mutations after neoadjuvant therapy. Cancer 2002; 94: 2055-62.
119. Grossi F, Loprevite M, Chiaramondia M, et al. Prognostic significance of K-ras, p53, bcl-2, PCNA, CD34 in radically resected non-small cell lung cancers. Eur J Cancer 2003; 39: 1242-50.
120. Huncharek M, Muscat J, Geschwind JF. K-ras oncogene mutation as a prognostic marker in non-small cell lung cancer: A combined analysis of 881 cases. Carcinogenesis 1999; 20: 1507-10.
121. Shigematsu H, Takahashi T, Nomura M, et al. Somatic mutations of the HER2 kinase domain in lung adenocarcinomas. Cancer Res 2005; 65: 1642-6.
122. Kosaka T, Yatabe Y, Endoh H, et al. Mutations of the epidermal growth factor receptor gene in lung cancer: biological and clinical implications. Cancer Res 2004; 64: 8919-23.
123. Yokoyama T, Kondo M, Goto Y, et al. EGFR point mutation in non-small cell lung cancer is occasionally accompanied by a second mutation or amplification. Cancer Sci 2006; 97: 753-9.
124. Suzuki M, Shigematsu H, Iizasa T, et al. Exclusive mutation in epidermal growth factor receptor gene, HER-2, and KRAS, and synchronous methylation of nonsmall cell lung cancer. Cancer 2006; 106: 2200-7.
125. Conde E, Angulo B, Tang M, et al. Molecular context of the EGFR mutations: evidence for the activation of mTOR/S6K signaling. Clin Cancer Res 2006; 12: 710-7.
126. Tsao M, Zhu C, Sakurada A, et al. An analysis of the prognostic and predictive importance of K-ras mutation status in the National Cancer Institute of Canada Clinical Trials Group BR.21 study of erlotinib versus placebo in the treatment of non-small cell lung cancer. Proc Am Soc Clin Oncol 2006; 24 (18s): 7005.
127. Stephens P, Hunter C, Bignell G, et al. Lung cancer: intragenic ERBB2 kinase mutations in tumours. Nature 2004; 431: 525-6.
128. Cappuzzo F, Bemis L, Varella-Garcia M. HER2 mutation and response to trastuzumab therapy in non-small-cell lung cancer. N Engl J Med 2006; 354: 2619-21.
129. Han SW, Kim TY, Jeon YK, et al. Optimization of patient selection for gefitinib in non-small cell lung cancer by combined analysis of epidermal growth factor receptor mutation, K-ras mutation, and Akt phosphorylation. Clin Cancer Res 2006; 12: 2538-44.
130. Pao W, Miller VA, Politi KA, et al. Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med 2005; 2: 1-11.
131. Balak MN, Gong Y, Riely GJ, et al. Novel D761Y and common secondary T790M mutations in epidermal growth factor receptor-mutant lung adenocarcinomas with acquired resistance to kinase inhibitors. Clin Cancer Res 2006; 12: 6494-501.
132. Chakravarti A, Loeffler JS, Dyson NJ. Insulin-like growth factor receptor I mediates resistance to anti-epidermal growth factor receptor therapy in primary human glioblastoma cells through continued activation of phosphoinositide 3-kinase signaling. Cancer Res 2002; 62: 200-7.
133. Cappuzzo F, Toschi L, Tallini G, et al. Insulin-like growth factor receptor 1 (IGFR-1) is significantly associated with longer survival in non-small cell lung cancer (NSCLC) patients treated with gefifinib. Ann Oncol 2006; 17: 1120-7.
134. Kwak EL, Sordella R, Bell DW, et al. Irreversible inhibitors of the EGF receptor may circumvent acquired resistance to gefitinib. Proc Natl Acad Sci USA 2005; 102: 7665-70.