Skip to main content
SpringerLink
Log in

Tyrosine Kinase Inhibitors and Cancer Therapy

  • Chapter
Targeted Interference with Signal Transduction Events

Part of the book series: Resent Results in Cancer Research ((RECENTCANCER,volume 172))

Abstract

Cancer is the second leading cause of death in the western world and is an increasing health problem in the developing world. Overall survival of patients with advanced cancer is poor. Until recently, surgery, chemotherapy, radiotherapy and endocrine therapy have been the mainstay in the treatment of cancer patients. This has improved outcomes in certain tumour types but treatment-related toxicity and emergence of drug resistance have been the major cause of morbidity and mortality. This need to improve outcomes has stimulated intense scientific research in recent years. Several novel drug targets have been identified. Amongst these, tyrosine kinases have emerged as the new promising anti-cancer drug target. Inhibitors of BCR-ABL, EGFR and VEGFR tyrosine kinases have now been licenced for use in cancers. In this chapter, we will discuss how this has been achieved in recent years.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 159.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Agus DB et al. (2000a) A potential role for activated HER-2 in prostate cancer. Semin Oncol 27:76–83; discussion 92–100

    PubMed  CAS  Google Scholar 

  • Agus DB et al. (2000b) HER-2/neu as a therapeutic target in non-small cell lung cancer, prostate cancer, and ovarian cancer. Semin Oncol 27:53–63; discussion 92–100

    PubMed  CAS  Google Scholar 

  • Agus DB, Gordon M, Taylor RB, Natale B, Karlan B, Mendelson D, et al. (2003) Clinical activity in a phase I trial of HER-2 targeted rhuMAb 2C4 (pertuzumab) in patients with advanced solid tumours. In: Proc ASCO (abstract 771)

    Google Scholar 

  • Akita RW, Sliwkowski MX (2003) Preclinical studies with Erlotinib (Tarceva). Semin Oncol 30:15–24

    PubMed  CAS  Google Scholar 

  • Albanell J et al. (2002) Pharmacodynamic studies of the epidermal growth factor receptor inhibitor ZD1839 in skin from cancer patients: histopathologic and molecular consequences of receptor inhibition. J Clin Oncol 20:110–124

    PubMed  CAS  Google Scholar 

  • Albanell J et al. (2003) Mechanism of action of anti-HER2 monoclonal antibodies: scientific update on trastuzumab and 2C4. Adv Exp Med Biol 532:253–268

    PubMed  CAS  Google Scholar 

  • Aligayer H et al. (2002) Activation of Src kinase in primary colorectal carcinoma: an indicator of poor clinical prognosis. Cancer 94:344–351

    PubMed  Google Scholar 

  • Arinaga M et al. (2003) Clinical significance of vascular endothelial growth factor C and vascular endothelial growth factor receptor 3 in patients with nonsmall cell lung carcinoma. Cancer 97:457–464

    PubMed  CAS  Google Scholar 

  • Awada A et al. (2005) Phase I safety and pharmacokinetics of BAY 43-9006 administered for 21 days on/7 days off in patients with advanced, refractory solid tumours. Br J Cancer 92:1855–1861

    PubMed  CAS  Google Scholar 

  • Azzoli CG et al. (2002) Trastuzumab in the treatment of non-small cell lung cancer. Semin Oncol 29:59–65

    PubMed  CAS  Google Scholar 

  • Barbieri MA et al. (2004) Receptor tyrosine kinase signaling and trafficking-paradigms revisited. Curr Top Microbiol Immunol 286:1–20

    PubMed  CAS  Google Scholar 

  • Baselga J et al. (1993) Antitumor effects of doxorubicin in combination with anti-epidermal growth factor receptor monoclonal antibodies. J Natl Cancer Inst 85:1327–1333

    PubMed  CAS  Google Scholar 

  • Baselga J et al. (1996) Phase II study of weekly intravenous recombinant humanized anti-p185HER2 monoclonal antibody in patients with HER2/neu-overexpressing metastatic breast cancer. J Clin Oncol 14:737–744

    PubMed  CAS  Google Scholar 

  • Baselga J et al. (1998) Recombinant humanized anti-HER2 antibody (Herceptin) enhances the antitumor activity of paclitaxel and doxorubicin against HER2/neu overexpressing human breast cancer xenografts. Cancer Res 58:2825–2831

    PubMed  CAS  Google Scholar 

  • Baselga J et al. (2000a) Phase I studies of anti-epidermal growth factor receptor chimeric antibody C225 alone and in combination with cisplatin. J Clin Oncol 18:904–914

    PubMed  CAS  Google Scholar 

  • Baselga J et al. (2000b) Continuous administration of ZD1839 (Iressa), a novel oral epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), in patients with five selected tumor types:evidence of activity and good tolerability [Abstract No. 686]. In Proc ASCO (Vol. 19)

    Google Scholar 

  • Baselga J, Cortes J (2005) Epidermal growth factor receptor pathway inhibitors. Cancer Chemother Biol Response Modif 22:205–223

    PubMed  CAS  Google Scholar 

  • Baykal C et al. (2003) Overexpression of the c-Met/HGF receptor and its prognostic significance in uterine cervix carcinomas. Gynecol Oncol 88:123–129

    PubMed  CAS  Google Scholar 

  • Ben-Bassat H (2001) Biological activity of tyrosine kinase inhibitors: novel agents for psoriasis therapy. Curr Opin Investig Drugs 2:1539–1545

    PubMed  CAS  Google Scholar 

  • Berchuck A et al. (1990) Overexpression of HER-2/neu is associated with poor survival in advanced epithelial ovarian cancer. Cancer Res 50:4087–4091

    PubMed  CAS  Google Scholar 

  • Blackhall F et al. (2006) Where next for gefitinib in patients with lung cancer? Lancet Oncol 7:499–507

    PubMed  CAS  Google Scholar 

  • Blume-Jensen P, Hunter T (2001) Oncogenic kinase signalling. Nature 411:355–365

    PubMed  CAS  Google Scholar 

  • Bookman MA et al. (2003) Evaluation of monoclonal humanized anti-HER2 antibody, trastuzumab, in patients with recurrent or refractory ovarian or primary peritoneal carcinoma with overexpression of HER2: a phase II trial of the Gynecologic Oncology Group. J Clin Oncol 21:283–290

    PubMed  CAS  Google Scholar 

  • Bruns CJ et al. (2000) Epidermal growth factor receptor blockade with C225 plus gemcitabine results in regression of human pancreatic carcinoma growing orthotopically in nude mice by antiangiogenic mechanisms. Clin Cancer Res 6:1936–1948

    PubMed  CAS  Google Scholar 

  • Buchdunger E et al. (1996) Inhibition of the Abl proteintyrosine kinase in vitro and in vivo by a 2-phenylaminopyrimidine derivative. Cancer Res 56:100–104

    PubMed  CAS  Google Scholar 

  • Burris H 3rd et al. (2005) Phase I safety, pharmacokinetics, and clinical activity study of lapatinib (GW572016), a reversible dual inhibitor of epidermal growth factor receptor tyrosine kinases, in heavily pretreated patients with metastatic carcinomas. J Clin Oncol 23:5305–5313

    PubMed  CAS  Google Scholar 

  • Burtness B, Li Y, Flood W, Mattar BI, Forastiere AA (2002) Phase III trial comparing cisplatin (C) + placebo (P) + anti-epidermal growth factor antibody (EGF-R) C225 in patients (pts) with metastatic/recurrent head and neck cancer (HNC) [Abstract No. 901]. In Proc ASCO (Vol. 21)

    Google Scholar 

  • Care RS et al. (2003) Incidence and prognosis of c-KIT and FLT3 mutations in core binding factor (CBF) acute myeloid leukaemias. Br J Haematol 121:775–777

    PubMed  CAS  Google Scholar 

  • Carter P et al. (1992) Humanization of an anti-p185HER2 antibody for human cancer therapy. Proc Natl Acad Sci USA 89:4285–4289

    PubMed  CAS  Google Scholar 

  • Ciardiello F et al. (2000) Antitumor effect and potentiation of cytotoxic drugs activity in human cancer cells by ZD-1839 (Iressa), an epidermal growth factor receptor-selective tyrosine kinase inhibitor. Clin Cancer Res 6:2053–2063

    PubMed  CAS  Google Scholar 

  • Ciardiello F, Tortora G (2001) A novel approach in the treatment of cancer: targeting the epidermal growth factor receptor. Clin Cancer Res 7:2958–2970

    PubMed  CAS  Google Scholar 

  • Cobleigh MA et al. (1999) Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. J Clin Oncol 17:2639–2648

    PubMed  CAS  Google Scholar 

  • Cobleigh MA et al. (2003) A phase I/II dose-escalation trial of bevacizumab in previously treated metastatic breast cancer. Semin Oncol 30:117–124

    PubMed  CAS  Google Scholar 

  • Cohen MH et al. (2003) FDA drug approval summary: gefitinib (ZD1839) (Iressa) tablets. Oncologist 8:303–306

    PubMed  CAS  Google Scholar 

  • Cohen MH et al. (2004) United States Food and Drug Administration drug approval summary:gefitinib (ZD1839; Iressa) tablets. Clin Cancer Res 10:1212–1218

    PubMed  CAS  Google Scholar 

  • Cohen MH et al. (2005) FDA drug approval summary: erlotinib (Tarceva) tablets. Oncologist 10:461–466

    PubMed  CAS  Google Scholar 

  • Cools J et al. (2003) A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome. N Engl J Med 348:1201–1214

    PubMed  CAS  Google Scholar 

  • Cools J et al. (2005) Resistance to tyrosine kinase inhibitors: calling on extra forces. Drug Resist Update 8:119–129

    CAS  Google Scholar 

  • Cortes J et al. (2003) Results of imatinib mesylate therapy in patients with refractory or recurrent acute myeloid leukemia, high-risk myelodysplastic syndrome, and myeloproliferative disorders. Cancer 97:2760–2766

    PubMed  CAS  Google Scholar 

  • Cunningham D et al. (2004) Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 351:337–345

    PubMed  CAS  Google Scholar 

  • Curnow RT (1997) Clinical experience with CD64-directed immunotherapy. An overview. Cancer Immunol Immunother 45:210–215

    PubMed  CAS  Google Scholar 

  • Dagher R et al. (2002) Approval summary: imatinib mesylate in the treatment of metastatic and/or unresectable malignant gastrointestinal stromal tumors. Clin Cancer Res 8:3034–3038

    PubMed  CAS  Google Scholar 

  • Dancey J, Sausville EA (2003) Issues and progress with protein kinase inhibitors for cancer treatment. Nat Rev Drug Discov 2:296–313

    PubMed  CAS  Google Scholar 

  • Deininger M (2005) Resistance to imatinib: mechanisms and management. J Natl Compr Canc Netw 3:757–768

    PubMed  Google Scholar 

  • Demetri GD (2002) Identification and treatment of chemoresistant inoperable or metastatic GIST: experience with the selective tyrosine kinase inhibitor imatinib mesylate (STI571). Eur J Cancer 38Suppl 5:S52–S59

    PubMed  Google Scholar 

  • Doroshow JH (2005) Targeting EGFR in non-small-cell lung cancer. N Engl J Med 353:200–202

    PubMed  CAS  Google Scholar 

  • Druker BJ et al. (1996) Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nat Med 2:561–566

    PubMed  CAS  Google Scholar 

  • Druker BJ et al. (2001a) Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med 344:1031–1037

    PubMed  CAS  Google Scholar 

  • Druker BJ et al. (2001b) Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome. N Engl J Med 344:1038–1042

    PubMed  CAS  Google Scholar 

  • Druker BJ (2002) Imatinib and chronic myeloid leukemia: validating the promise of molecularly targeted therapy. Eur J Cancer 38Suppl 5:S70–S76

    PubMed  Google Scholar 

  • Dudek AZ et al. (2006) Skin rash and bronchoalveolar histology correlates with clinical benefit in patients treated with gefitinib as a therapy for previously treated advanced or metastatic non-small cell lung cancer. Lung Cancer 51:89–96

    PubMed  Google Scholar 

  • Eggert A et al. (2000) Prognostic and biological role of neurotrophin-receptor TrkA and TrkB in neuroblastoma. Klin Padiatr 212:200–205

    PubMed  CAS  Google Scholar 

  • Escudier B et al. (2005) Randomized phase III trial of the Raf kinase and VEGFR inhibitor sorafenib (BAY 43-9006) in patients with advanced renal cell carcinoma (RCC). Proc Am Soc Clin Oncol 23:1093s

    Google Scholar 

  • Faivre S et al. (2006) Safety, pharmacokinetic, and antitumor activity of SU11248, a novel oral multitarget tyrosine kinase inhibitor, in patients with cancer. J Clin Oncol 24:25–35

    PubMed  CAS  Google Scholar 

  • Fan Z et al. (1993) Antitumor effect of anti-epidermal growth factor receptor monoclonal antibodies plus cis-diamminedichloroplatinum on well established A431 cell xenografts. Cancer Res 53:4637–4642

    PubMed  CAS  Google Scholar 

  • Farah RA et al. (1998) The development of monoclonal antibodies for the therapy of cancer. Crit Rev Eukaryot Gene Expr 8:321–356

    PubMed  CAS  Google Scholar 

  • Ferrara N et al. (2004) Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer. Nat Rev Drug Discov 3:391–400

    PubMed  CAS  Google Scholar 

  • Ferrara N et al. (2005) Bevacizumab (Avastin), a humanized anti-VEGF monoclonal antibody for cancer therapy. Biochem Biophys Res Commun 333:328–335

    PubMed  CAS  Google Scholar 

  • Ferrara N. and Kerbel RS (2005) Angiogenesis as a therapeutic target. Nature 438:967–974

    PubMed  CAS  Google Scholar 

  • Fischer OM et al. (2003) EGFR signal transactivation in cancer cells. Biochem Soc Trans 31:1203–1208

    PubMed  CAS  Google Scholar 

  • Fox SB et al. (2001) Angiogenesis: pathological, prognostic, and growth-factor pathways and their link to trial design and anticancer drugs. Lancet Oncol 2:278–289

    PubMed  CAS  Google Scholar 

  • Frieze DA, McCune JS (2006) Current status of cetuximab for the treatment of patients with solid tumors. Ann Pharmacother 40:241–250

    PubMed  CAS  Google Scholar 

  • Fry DW (2003) Mechanism of action of erbB tyrosine kinase inhibitors. Exp Cell Res 284:131–139

    PubMed  CAS  Google Scholar 

  • Fukuoka M, Yano S, Giaccone G, Tanura T, Nakagawa K, Douillard J et al. (2002) Final results from a phase II trial of ZD1839 (Iressa) for patients with advanced non-small cell lung cancer (IDEAL 1) [Abstract No. 1188]. In Proc ASCO (Vol. 21)

    Google Scholar 

  • Gascoyne RD et al. (1999) Prognostic significance of anaplastic lymphoma kinase (ALK) protein expression in adults with anaplastic large cell lymphoma. Blood 93:3913–3921

    PubMed  CAS  Google Scholar 

  • Giaccone G et al. (2004) Gefitinib in combination with gemcitabine and cisplatin in advanced non-smallcell lung cancer:a phase III trial-INTACT 1. J Clin Oncol 22:777–784

    PubMed  CAS  Google Scholar 

  • Gilbert CW et al. (2003) Targeted prodrug treatment of HER-2-positive breast tumor cells using trastuzumab and paclitaxel linked by A-Z-CINN Linker. J Exp Ther Oncol 3:27–35

    PubMed  CAS  Google Scholar 

  • Gleich GJ et al. (2002) Treatment of hypereosinophilic syndrome with imatinib mesilate. Lancet 359:1577–1578

    PubMed  CAS  Google Scholar 

  • Gleissner B et al. (2002) Leading prognostic relevance of the BCR-ABL translocation in adult acute B-lineage lymphoblastic leukemia:a prospective study of the German Multicenter Trial Group and confirmed polymerase chain reaction analysis. Blood 99:1536–1543

    PubMed  CAS  Google Scholar 

  • Goldberg RM (2005) Cetuximab. Nat Rev Drug Discov Suppl:S10–S11

    Google Scholar 

  • Gordon MS et al. (2001) Phase I safety and pharmacokinetic study of recombinant human anti-vascular endothelial growth factor in patients with advanced cancer. J Clin Oncol 19:843–850

    PubMed  CAS  Google Scholar 

  • Goss GD, Hirte H, Lorimer I, Miller W, Stewart DJ, Batish G et al. (2001) Final results of the dose escalation phase of a phase I pharmacokinetic (PK), pharmacodynamic (PD) and biological activity study of ZD1839:NCIC CTG Ind.122 [Abstract No. 335]. In Proc ASCO (Vol. 20)

    Google Scholar 

  • Grandis JR et al. (1998) Downmodulation of TGF-alpha protein expression with antisense oligonucleotides inhibits proliferation of head and neck squamous carcinoma but not normal mucosal epithelial cells. J Cell Biochem 69:55–62

    PubMed  CAS  Google Scholar 

  • Grunwald V, Hidalgo M (2003a) Development of the epidermal growth factor receptor inhibitor OSI-774. Semin Oncol 30:23–31

    PubMed  CAS  Google Scholar 

  • Grunwald V, Hidalgo M (2003b) Developing inhibitors of the epidermal growth factor receptor for cancer treatment. J Natl Cancer Inst 95:851–867

    PubMed  Google Scholar 

  • Gunby RH et al. (2003) Sensitivity to imatinib but low frequency of the TEL/PDGFRb fusion protein in chronic myelomonocytic leukemia. Haematologica 88:408–415

    PubMed  CAS  Google Scholar 

  • Hambek M et al. (2001) Tumor necrosis factor alpha sensitizes low epidermal growth factor receptor (EGFR)-expressing carcinomas for anti-EGFR therapy. Cancer Res 61:1045–1049

    PubMed  CAS  Google Scholar 

  • Harari PM, Huang SM (2001) Radiation response modification following molecular inhibition of epidermal growth factor receptor signaling. Semin Radiat Oncol 11:281–289

    PubMed  CAS  Google Scholar 

  • Harries M, Smith I (2002) The development and clinical use of trastuzumab (Herceptin). Endocr Relat Cancer 9:75–85

    PubMed  CAS  Google Scholar 

  • Herbst RS (2003) Erlotinib (Tarceva): an update on the clinical trial program. Semin Oncol 30:34–46

    PubMed  CAS  Google Scholar 

  • Herbst RS et 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

    PubMed  CAS  Google Scholar 

  • Herbst RS et al. (2005) 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 23:5892–5899

    PubMed  CAS  Google Scholar 

  • Heymach JV (2005) ZD6474-clinical experience to date. Br J Cancer 92Suppl 1:S14–S20

    PubMed  CAS  Google Scholar 

  • Hidalgo M et al. (2001) Phase I and pharmacologic study of OSI-774, an epidermal growth factor receptor tyrosine kinase inhibitor, in patients with advanced solid malignancies. J Clin Oncol 19:3267–3279

    PubMed  CAS  Google Scholar 

  • Hirata A et al. (2002) ZD1839 (Iressa) induces antiangiogenic effects through inhibition of epidermal growth factor receptor tyrosine kinase. Cancer Res 62: 2554–2560

    PubMed  CAS  Google Scholar 

  • Hoffmann T et al. (1997) Antitumor activity of anti-epidermal growth factor receptor monoclonal antibodies and cisplatin in ten human head and neck squamous cell carcinoma lines. Anticancer Res 17:4419–4425

    PubMed  CAS  Google Scholar 

  • Holash J et al. (2002) VEGF-Trap: a VEGF blocker with potent antitumor effects. Proc Natl Acad Sci USA 99:11393–11398

    PubMed  CAS  Google Scholar 

  • Homer JJ et al. (2002) Soluble Tie-2 receptor levels independently predict locoregional recurrence in head and neck squamous cell carcinoma. Head Neck 24:773–778

    PubMed  Google Scholar 

  • Hortobagyi GN (2005) Trastuzumab in the treatment of breast cancer. N Engl J Med 353:1734–1736

    PubMed  CAS  Google Scholar 

  • Huang SM, Harari PM (2000) Modulation of radiation response after epidermal growth factor receptor blockade in squamous cell carcinomas: inhibition of damage repair, cell cycle kinetics, and tumor angiogenesis. Clin Cancer Res 6:2166–2174

    PubMed  CAS  Google Scholar 

  • Hudson PJ (1999) Recombinant antibody constructs in cancer therapy. Curr Opin Immunol 11:548–557

    PubMed  CAS  Google Scholar 

  • Hunter T (1998) The Croonian Lecture 1997. The phosphorylation of proteins on tyrosine: its role in cell growth and disease. Philos Trans R Soc Lond B Biol Sci 353:583–605

    PubMed  CAS  Google Scholar 

  • Hunter T (2000) Signaling-2000 and beyond. Cell 100:113–127

    PubMed  CAS  Google Scholar 

  • Hurwitz H et al. (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350:2335–2342

    PubMed  CAS  Google Scholar 

  • Hurwitz HI et al. (2005) Bevacizumab in combination with fluorouracil and leucovorin:an active regimen for first-line metastatic colorectal cancer. J Clin Oncol 23:3502–3508

    PubMed  CAS  Google Scholar 

  • Hynes NE, Lane HA (2005) ERBB receptors and cancer: the complexity of targeted inhibitors. Nat Rev Cancer 5:341–354

    PubMed  CAS  Google Scholar 

  • Indo Y (2002) Genetics of congenital insensitivity to pain with anhidrosis (CIPA) or hereditary sensory and autonomic neuropathy type IV. Clinical, biological and molecular aspects of mutations in TRKA(NTRK1) gene encoding the receptor tyrosine kinase for nerve growth factor. Clin Auton Res 12Suppl 1:I20–I32

    PubMed  Google Scholar 

  • Inoue A et al. (2006) 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 24:3340–3346

    PubMed  CAS  Google Scholar 

  • James ND et al. (2001) A phase II study of the bispecific antibody MDX-H210 (anti-HER2 x CD64) with GMCSF in HER2+ advanced prostate cancer. Br J Cancer 85:152–156

    PubMed  CAS  Google Scholar 

  • Johnson DH (2003) Gefitinib (Iressa) trials in non-small cell lung cancer. Lung Cancer 41Suppl 1:S23–S28

    PubMed  Google Scholar 

  • Johnson DH et al. (2004) Randomized phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol 22:2184–2191

    PubMed  CAS  Google Scholar 

  • Johnson JR et al. (2003) Approval summary: Imatinib mesylate capsules for treatment of adult patients with newly diagnosed Philadelphia chromosome-positive chronic myelogenous leukemia in chronic phase. Clin Cancer Res 9:1972–1979

    PubMed  CAS  Google Scholar 

  • Johnson JR et al. (2005) Approval summary for erlotinib for treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of at least one prior chemotherapy regimen. Clin Cancer Res 11:6414–6421

    PubMed  CAS  Google Scholar 

  • Kabbinavar F et al. (2003) Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer. J Clin Oncol 21:60–65

    PubMed  CAS  Google Scholar 

  • Kakiuchi S et al. (2004) Prediction of sensitivity of advanced non-small cell lung cancers to gefitinib (Iressa, ZD1839). Hum Mol Genet 13:3029–3043

    PubMed  CAS  Google Scholar 

  • Kantarjian H et al. (2006) Dasatinib. Nat Rev Drug Discov 5:717–718

    PubMed  CAS  Google Scholar 

  • Krause DS, Van Etten RA (2005) Tyrosine kinases as targets for cancer therapy. N Engl J Med 353:172–187

    PubMed  CAS  Google Scholar 

  • Kris MG et al. (2002) A phase II trial of ZD1839 (Iressa) in advanced non-small cell lung cancer (NSCLC) patients who failed platinum-and docetaxel-based regimens (IDEAL 2) [Abstract No. 1166]. In Proc ASCO (Vol. 21)

    Google Scholar 

  • Krupa A, Srinivasan N (2002) The repertoire of protein kinases encoded in the draft version of the human genome:atypical variations and uncommon domain combinations. Genome Biol 3:RESEARCH0066

    Google Scholar 

  • Kuenen BC et al. (2002) Dose-finding and pharmacokinetic study of cisplatin, gemcitabine, and SU5416 in patients with solid tumors. J Clin Oncol 20:1657–1667

    PubMed  CAS  Google Scholar 

  • Kupsch P et al. (2005) Results of a phase I trial of sorafenib (BAY 43-9006) in combination with oxaliplatin in patients with refractory solid tumors, including colorectal cancer. Clin Colorectal Cancer 5:188–196

    PubMed  Google Scholar 

  • Laird AD, Cherrington JM (2003) Small molecule tyrosine kinase inhibitors: clinical development of anticancer agents. Expert Opin Investig Drugs 12:51–64

    PubMed  CAS  Google Scholar 

  • Lau SC et al. (2005) Technology evaluation:VEGF Trap (cancer), Regeneron/sanofi-aventis. Curr Opin Mol Ther 7:493–501

    PubMed  Google Scholar 

  • le Coutre P et al. (1999) In vivo eradication of human BCR/ABL-positive leukemia cells with an ABL kinase inhibitor. J Natl Cancer Inst 91:163–168

    PubMed  Google Scholar 

  • Lee DC et al. (2002) RET receptor tyrosine kinase isoforms in kidney function and disease. Oncogene 21:5582–5592

    PubMed  CAS  Google Scholar 

  • Lewis LD et al. (2001) Pharmacokinetic-pharmacodynamic relationships of the bispecific antibody MDX-H210 when administered in combination with interferon gamma:a multiple-dose phase-I study in patients with advanced cancer which overexpresses HER-2/neu. J Immunol Methods 248:149–165

    PubMed  CAS  Google Scholar 

  • Lin WC et al. (1999) tie-1 protein tyrosine kinase: a novel independent prognostic marker for gastric cancer. Clin Cancer Res 5:1745–1751

    PubMed  CAS  Google Scholar 

  • Lynch DH, Yang XD (2002) Therapeutic potential of ABX-EGF: a fully human anti-epidermal growth factor receptor monoclonal antibody for cancer treatment. Semin Oncol 29:47–50

    PubMed  CAS  Google Scholar 

  • Lynch TJ et al. (2004) 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

    PubMed  CAS  Google Scholar 

  • Madhusudan S, Ganesan TS (2004) Tyrosine kinase inhibitors in cancer therapy. Clin Biochem 37:618–635

    PubMed  CAS  Google Scholar 

  • Manley PW et al. (2002) Imatinib: a selective tyrosine kinase inhibitor. Eur J Cancer 38Suppl 5:S19–S27

    PubMed  Google Scholar 

  • Manning G et al. (2002) The protein kinase complement of the human genome. Science 298:1912–1934

    PubMed  CAS  Google Scholar 

  • Margolin K et al. (2001) Phase Ib trial of intravenous recombinant humanized monoclonal antibody to vascular endothelial growth factor in combination with chemotherapy in patients with advanced cancer:pharmacologic and long-term safety data. J Clin Oncol 19:851–856

    PubMed  CAS  Google Scholar 

  • Meden H, Kuhn W. (1997) Overexpression of the oncogene c-erbB-2 (HER2/neu) in ovarian cancer:a new prognostic factor. Eur J Obstet Gynecol Reprod Biol 71:173–179

    PubMed  CAS  Google Scholar 

  • Mendelsohn J. (2002) Targeting the epidermal growth factor receptor for cancer therapy. J Clin Oncol 20:1S–13S

    PubMed  CAS  Google Scholar 

  • Mendelsohn J, Shin DM, Donato N, Khuri F, Radinsky R et al. (1999) A phase I study of chimerized antiepidermal growth factor receptor (EGFr) monoclonal antibody, C225, in combination with cisplatin (CDDP) in patients (PTS) with recurrent head and neck squamous cell carcinoma (SCC) [Abstract No.1502]. In Proc ASCO 1999 (Vol. 18)

    Google Scholar 

  • Meunier-Carpentier S et al. (2005) Comparison of the prognosis indication of VEGFR-1 and VEGFR-2 and Tie2 receptor expression in breast carcinoma. Int J Oncol 26:977–984

    PubMed  CAS  Google Scholar 

  • Miyazaki T et al. (2003) FAK overexpression is correlated with tumour invasiveness and lymph node metastasis in oesophageal squamous cell carcinoma. Br J Cancer 89:140–145

    PubMed  CAS  Google Scholar 

  • Mohamed MK et al. (2005) Skin rash and good performance status predict improved survival with gefitinib in patients with advanced non-small cell lung cancer. Ann Oncol 16:780–785

    PubMed  CAS  Google Scholar 

  • Moore M et al. (2005) Phase I study to determine the safety and pharmacokinetics of the novel Raf kinase and VEGFR inhibitor BAY 43-9006, administered for 28 days on/7 days off in patients with advanced, refractory solid tumors. Ann Oncol 16:1688–1694

    PubMed  CAS  Google Scholar 

  • Motzer RJ et al. (2006) Activity of SU11248, a multitargeted inhibitor of vascular endothelial growth factor receptor and platelet-derived growth factor receptor, in patients with metastatic renal cell carcinoma. J Clin Oncol 24:16–24

    PubMed  CAS  Google Scholar 

  • Moyer J.D et al. (1997) Induction of apoptosis and cell cycle arrest by CP-358,774, an inhibitor of epidermal growth factor receptor tyrosine kinase. Cancer Res 57:4838–4848

    PubMed  CAS  Google Scholar 

  • Naeem M et al. (2002) Analysis of c-kit protein expression in small-cell lung carcinoma and its implication for prognosis. Hum Pathol 33:1182–1187

    PubMed  CAS  Google Scholar 

  • Neet K, Hunter, T. (1996) Vertebrate non-receptor protein-tyrosine kinase families. Genes Cells 1:147–169

    PubMed  CAS  Google Scholar 

  • Negoro S, Nakagawa K, Fukuoka M, Kudoh S, Tamura T, Yoshimura N et al. (2001) Final results of a phase I intermittent dose-escalation trial of ZD1839 (‘Iressa’) in Japanese patients with various solid tumours [Abstract No. 1292]. In Proc ASCO (Vol. 20)

    Google Scholar 

  • Nelson MH, Dolder, C.R. (2006) Lapatinib:a novel dual tyrosine kinase inhibitor with activity in solid tumors. Ann Pharmacother 40:261–269

    PubMed  CAS  Google Scholar 

  • Ng EW et al. (2006) Pegaptanib, a targeted anti-VEGF aptamer for ocular vascular disease. Nat Rev Drug Discov 5:123–132

    PubMed  CAS  Google Scholar 

  • Ng SS et al. (2002) Effects of the epidermal growth factor receptor inhibitor OSI-774, Tarceva, on downstream signaling pathways and apoptosis in human pancreatic adenocarcinoma. Mol Cancer Ther 1:777–783

    PubMed  CAS  Google Scholar 

  • Nicholson RI et al. (2001) EGFR and cancer prognosis. Eur J Cancer 37Suppl 4:S9–S15

    PubMed  CAS  Google Scholar 

  • Normanno N et al. (2002) Cooperative inhibitory effect of ZD1839 (Iressa) in combination with trastuzumab (Herceptin) on human breast cancer cell growth. Ann Oncol 13:65–72

    PubMed  CAS  Google Scholar 

  • Normanno N et al. (2006) Epidermal growth factor receptor (EGFR) signaling in cancer. Gene 366:2–16

    PubMed  CAS  Google Scholar 

  • Oda Y et al. (2000) Expression of hepatocyte growth factor (HGF)/scatter factor and its receptor c-MET correlates with poor prognosis in synovial sarcoma. Hum Pathol 31:185–192

    PubMed  CAS  Google Scholar 

  • Ozvegy-Laczka C et al. (2005) Tyrosine kinase inhibitor resistance in cancer:role of ABC multidrug transporters. Drug Resist Update 8, 15–26

    Google Scholar 

  • Pal SK, Pegram M (2005) Epidermal growth factor receptor and signal transduction: potential targets for anticancer therapy. Anticancer Drugs 16:483–494

    PubMed  CAS  Google Scholar 

  • Pao W et al. (2004) EGF receptor gene mutations are common in lung cancers from “never smokers” and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc Natl Acad Sci USA 101:13306–13311

    PubMed  CAS  Google Scholar 

  • Pardanani A et al. (2003) CHIC2 deletion, a surrogate for FIP1L1-PDGFRA fusion, occurs in systemic mastocytosis associated with eosinophilia and predicts response to imatinib mesylate therapy. Blood 102:3093–3096

    PubMed  CAS  Google Scholar 

  • Parr C, Jiang WG (2003) Quantitative analysis of lymphangiogenic markers in human colorectal cancer. Int J Oncol 23:533–539

    PubMed  CAS  Google Scholar 

  • Paterson SC et al. (2003) Is there a cloud in the silver lining for imatinib? Br J Cancer 88:983–987

    PubMed  CAS  Google Scholar 

  • Pegram MD et al. (1998a) HER-2/neu as a predictive marker of response to breast cancer therapy. Breast Cancer Res Treat 52:65–77

    PubMed  CAS  Google Scholar 

  • Pegram MD et al. (1998b) Phase II study of receptor-enhanced chemosensitivity using recombinant humanized anti-p185HER2/neu monoclonal antibody plus cisplatin in patients with HER2/neu-overexpressing metastatic breast cancer refractory to chemotherapy treatment. J Clin Oncol 16:2659–2671

    PubMed  CAS  Google Scholar 

  • Pegram MD et al. (2000) Trastuzumab and chemotherapeutics: drug interactions and synergies. Semin Oncol 27:21–25; discussion 92–100

    PubMed  CAS  Google Scholar 

  • Penne K et al. (2005) Gefitinib (Iressa, ZD1839) and tyrosine kinase inhibitors:the wave of the future in cancer therapy. Cancer Nurs 28:481–486

    PubMed  Google Scholar 

  • Perrotte P et al. (1999) Anti-epidermal growth factor receptor antibody C225 inhibits angiogenesis in human transitional cell carcinoma growing orthotopically in nude mice. Clin Cancer Res 5:257–265

    PubMed  CAS  Google Scholar 

  • Peters G et al. (2003) IGF-1R, IGF-1 and IGF-2 expression as potential prognostic and predictive markers in colorectal-cancer. Virchows Arch

    Google Scholar 

  • Piccart-Gebhart MJ et al. (2005) Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 353:1659–1672

    PubMed  CAS  Google Scholar 

  • Pollack VA et al. (1999) Inhibition of epidermal growth factor receptor-associated tyrosine phosphorylation in human carcinomas with CP-358,774:dynamics of receptor inhibition in situ and antitumor effects in athymic mice. J Pharmacol Exp Ther 291:739–748

    PubMed  CAS  Google Scholar 

  • Posey JA et al. (1999) A pilot trial of GM-CSF and MDXH210 in patients with erbB-2-positive advanced malignancies. J Immunother 22:371–379

    PubMed  CAS  Google Scholar 

  • Prenen H et al. (2006) Efficacy of the kinase inhibitor SU11248 against gastrointestinal stromal tumor mutants refractory to imatinib mesylate. Clin Cancer Res 12:2622–2627

    PubMed  CAS  Google Scholar 

  • Press MF et al. (1997) HER-2/neu gene amplification characterized by fluorescence in situ hybridization: poor prognosis in node-negative breast carcinomas. J Clin Oncol 15:2894–2904

    PubMed  CAS  Google Scholar 

  • Ranson M et al. (2002) ZD1839, a selective oral epidermal growth factor receptor-tyrosine kinase inhibitor, is well tolerated and active in patients with solid, malignant tumors:results of a phase I trial. J Clin Oncol 20:2240–2250

    PubMed  CAS  Google Scholar 

  • Ranson M (2004) Epidermal growth factor receptor tyrosine kinase inhibitors. Br J Cancer 90:2250–2255

    PubMed  CAS  Google Scholar 

  • Ratain MJ et al. (2006) Phase II placebo-controlled randomized discontinuation trial of sorafenib in patients with metastatic renal cell carcinoma. J Clin Oncol 24:2505–2512

    PubMed  CAS  Google Scholar 

  • Rhee J, Hoff PM (2005) Angiogenesis inhibitors in the treatment of cancer. Expert Opin Pharmacother 6:1701–1711

    PubMed  CAS  Google Scholar 

  • Richly H et al. (2006) Results of a Phase I trial of sorafenib (BAY 43-9006) in combination with doxorubicin in patients with refractory solid tumors. Ann Oncol 17:866–873

    PubMed  CAS  Google Scholar 

  • Rini BI (2006) Sorafenib. Expert Opin Pharmacother 7:453–461

    PubMed  CAS  Google Scholar 

  • Robert C et al. (2005) Cutaneous side-effects of kinase inhibitors and blocking antibodies. Lancet Oncol 6:491–500

    PubMed  CAS  Google Scholar 

  • Robinson DR et al. (2000) The protein tyrosine kinase family of the human genome. Oncogene 19:5548–5557

    PubMed  CAS  Google Scholar 

  • Rochlitz C et al. (1999) Axl expression is associated with adverse prognosis and with expression of Bcl-2 and CD34 in de novo acute myeloid leukemia (AML): results from a multicenter trial of the Swiss Group for Clinical Cancer Research (SAKK). Leukemia 13:1352–1358

    PubMed  CAS  Google Scholar 

  • Romond EH et al. (2005) Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 353:1673–1684

    PubMed  CAS  Google Scholar 

  • Rubin BP et al. (2001) KIT activation is a ubiquitous feature of gastrointestinal stromal tumors. Cancer Res 61:8118–8121

    PubMed  CAS  Google Scholar 

  • Ryan AJ, Wedge SR (2005) ZD6474-a novel inhibitor of VEGFR and EGFR tyrosine kinase activity. Br J Cancer 92Suppl 1:S6–S13

    PubMed  CAS  Google Scholar 

  • Sadasivan R et al. (1993) Overexpression of Her-2/neu may be an indicator of poor prognosis in prostate cancer. J Urol 150:126–131

    PubMed  CAS  Google Scholar 

  • Saijo N, Nishio KN (2003) (Abstract no. O.20) Mechanisms of ZD1839 resistance and ZD1839 induced pulmonary fibrosis. In 2nd International Symposium on Signal Transduction Modulators in Cancer Therapy.

    Google Scholar 

  • Sakurada A et al. (2006) Epidermal growth factor receptor tyrosine kinase inhibitors in lung cancer: impact of primary or secondary mutations. Clin Lung Cancer 7Suppl 4:S138–S144

    PubMed  CAS  Google Scholar 

  • Saltz LB et al. (2004) Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor. J Clin Oncol 22:1201–1208

    PubMed  CAS  Google Scholar 

  • Sato JD et al. (1983) Biological effects in vitro of monoclonal antibodies to human epidermal growth factor receptors. Mol Biol Med 1:511–529

    PubMed  CAS  Google Scholar 

  • Sawyers CL (1999) Chronic myeloid leukemia. N Engl J Med 340:1330–1340

    PubMed  CAS  Google Scholar 

  • Sawyers CL (2002) Imatinib GIST keeps finding new indications: successful treatment of dermatofibrosarcoma protuberans by targeted inhibition of the platelet-derived growth factor receptor. J Clin Oncol 20:3568–3569

    PubMed  Google Scholar 

  • Schlessinger J (2000) Cell signaling by receptor tyrosine kinases. Cell 103:211–225

    PubMed  CAS  Google Scholar 

  • Schnittger S et al. (2002) Analysis of FLT3 length mutations in 1003 patients with acute myeloid leukemia: correlation to cytogenetics, FAB subtype, and prognosis in the AMLCG study and usefulness as a marker for the detection of minimal residual disease. Blood 100:59–66

    PubMed  CAS  Google Scholar 

  • Selvaggi G et al. (2002) HER-2/neu overexpression in patients with radically resected nonsmall cell lung carcinoma. Impact on long-term survival. Cancer 94:2669–2674

    PubMed  Google Scholar 

  • Shepherd FA et al. (2005) Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med 353:123–132

    PubMed  CAS  Google Scholar 

  • Shin DM et al. (2001) Epidermal growth factor receptor-targeted therapy with C225 and cisplatin in patients with head and neck cancer. Clin Cancer Res 7:1204–1213

    PubMed  CAS  Google Scholar 

  • Sirotnak FM (2003) Studies with ZD1839 in preclinical models. Semin Oncol 30:12–20

    PubMed  CAS  Google Scholar 

  • Sirotnak FM et al. (2000) Efficacy of cytotoxic agents against human tumor xenografts is markedly enhanced by coadministration of ZD1839 (Iressa), an inhibitor of EGFR tyrosine kinase. Clin Cancer Res 6:4885–4892

    PubMed  CAS  Google Scholar 

  • Slamon DJ et al. (1987) Human breast cancer:correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235:177–182

    PubMed  CAS  Google Scholar 

  • Slamon DJ et al. (1989) Studies of the HER-2/neu protooncogene in human breast and ovarian cancer. Science 244:707–712

    PubMed  CAS  Google Scholar 

  • Slamon DJ et al. (2001) Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 344:783–792

    PubMed  CAS  Google Scholar 

  • Small EJ et al. (2001) Docetaxel, estramustine, plus trastuzumab in patients with metastatic androgenindependent prostate cancer. Semin Oncol 28:71–76

    PubMed  CAS  Google Scholar 

  • Smith J. (2005) Erlotinib: small-molecule targeted therapy in the treatment of non-small-cell lung cancer. Clin Ther 27:1513–1534

    PubMed  CAS  Google Scholar 

  • Speake G et al. (2005) Recent developments related to the EGFR as a target for cancer chemotherapy. Curr Opin Pharmacol 5:343–349

    PubMed  CAS  Google Scholar 

  • Spector NL et al. (2005) Study of the biologic effects of lapatinib, a reversible inhibitor of ErbB1 and ErbB2 tyrosine kinases, on tumor growth and survival pathways in patients with advanced malignancies. J Clin Oncol 23:2502–2512

    PubMed  CAS  Google Scholar 

  • Stamos J et al. (2002) Structure of the epidermal growth factor receptor kinase domain alone and in complex with a 4-anilinoquinazoline inhibitor. J Biol Chem 277:46265–46272

    PubMed  CAS  Google Scholar 

  • Storniolo A et al. (2005) A Phase I, open-label study of lapatinib (GW572016) plus trastuzumab;a clinically active regimen (abstract). Proc Am Soc Clin Oncol 23:559

    Google Scholar 

  • Strumberg D. (2005) Preclinical and clinical development of the oral multikinase inhibitor sorafenib in cancer treatment. Drugs Today (Barc) 41:773–784

    CAS  Google Scholar 

  • Strumberg D et al. (2005) Phase I clinical and pharmacokinetic study of the novel Raf kinase and vascular endothelial growth factor receptor inhibitor BAY 43-9006 in patients with advanced refractory solid tumors. J Clin Oncol 23:965–972

    PubMed  CAS  Google Scholar 

  • Talpaz M et al. (2006) Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias. N Engl J Med 354:2531–2541

    PubMed  CAS  Google Scholar 

  • Tandon AK et al. (1989) HER-2/neu oncogene protein and prognosis in breast cancer. J Clin Oncol 7:1120–1128

    PubMed  CAS  Google Scholar 

  • Taniguchi M et al. (1999) Effect of c-kit mutation on prognosis of gastrointestinal stromal tumors. Cancer Res 59:4297–4300

    PubMed  CAS  Google Scholar 

  • Thatcher N et al. (2005) 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 366:1527–1537

    PubMed  CAS  Google Scholar 

  • Thomas A.L et al. (2005) Phase I study of the safety, tolerability, pharmacokinetics, and pharmacodynamics of PTK787/ZK 222584 administered twice daily in patients with advanced cancer. J Clin Oncol 23:4162–4171

    PubMed  CAS  Google Scholar 

  • Tibes R et al. (2005) Tyrosine kinase inhibitors and the dawn of molecular cancer therapeutics. Annu Rev Pharmacol Toxicol 45:357–384

    PubMed  CAS  Google Scholar 

  • Toyama T et al. (2003) Reduced expression of the Syk gene is correlated with poor prognosis in human breast cancer. Cancer Lett 189:97–102

    PubMed  CAS  Google Scholar 

  • Tsai CM et al. (1993) Correlation of intrinsic chemoresistance of non-small-cell lung cancer cell lines with HER-2/neu gene expression but not with ras gene mutations. J Natl Cancer Inst 85:897–901

    PubMed  CAS  Google Scholar 

  • Tsao MS et al. (2005) Erlotinib in lung cancer — molecular and clinical predictors of outcome. N Engl J Med 353:133–144

    PubMed  CAS  Google Scholar 

  • Tuveson DA et al. (2001) STI571 inactivation of the gastrointestinal stromal tumor c-KIT oncoprotein: biological and clinical implications. Oncogene 20:5054–5058

    PubMed  CAS  Google Scholar 

  • Tyagi P. (2005) Vatalanib (PTK787/ZK 222584) in combination with FOLFOX4 versus FOLFOX4 alone as first-line treatment for colorectal cancer: preliminary results from the CONFIRM-1 trial. Clin Colorectal Cancer 5:24–26

    PubMed  Google Scholar 

  • Ueki T et al. (1997) Expression of hepatocyte growth factor and its receptor c-met proto-oncogene in hepatocellular carcinoma. Hepatology 25:862–866

    PubMed  CAS  Google Scholar 

  • van der Kuip H et al. (2005) Mechanisms of clinical resistance to small molecule tyrosine kinase inhibitors targeting oncogenic tyrosine kinases. Am J Pharmacogenomics 5:101–112

    PubMed  Google Scholar 

  • Verstovsek S et al. (2002) Prognostic significance of Tie-1 protein expression in patients with early chronic phase chronic myeloid leukemia. Cancer 94:1517–1521

    PubMed  CAS  Google Scholar 

  • Vogel CL et al. (2002) Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-over-expressing metastatic breast cancer. J Clin Oncol 20:719–726

    PubMed  CAS  Google Scholar 

  • Weiner HL, Zagzag D (2000) Growth factor receptor tyrosine kinases:cell adhesion kinase family suggests a novel signaling mechanism in cancer. Cancer Invest 18:544–554

    PubMed  CAS  Google Scholar 

  • Wells A (2000) Tumor invasion:role of growth factorinduced cell motility. Adv Cancer Res 78:31–101

    PubMed  CAS  Google Scholar 

  • Wood JM et al. (2000) PTK787/ZK 222584, a novel and potent inhibitor of vascular endothelial growth factor receptor tyrosine kinases, impairs vascular endothelial growth factor-induced responses and tumor growth after oral administration. Cancer Res 60:2178–2189

    PubMed  CAS  Google Scholar 

  • Yang JC et al. (2003) A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N Engl J Med 349:427–434

    PubMed  CAS  Google Scholar 

  • Yang JC (2004) Bevacizumab for patients with metastatic renal cancer: an update. Clin Cancer Res 10:6367S–6370S

    PubMed  CAS  Google Scholar 

  • Yarden Y, Sliwkowski MX (2001) Untangling the ErbB signalling network. Nat Rev Mol Cell Biol 2:127–137

    PubMed  CAS  Google Scholar 

  • Zaczek A et al. (2005) The diverse signaling network of EGFR, HER2, HER3 and HER4 tyrosine kinase receptors and the consequences for therapeutic approaches. Histol Histopathol 20:1005–1015

    PubMed  CAS  Google Scholar 

  • Zakarija A, Soff G (2005) Update on angiogenesis inhibitors. Curr Opin Oncol 17:578–583

    PubMed  CAS  Google Scholar 

  • Zhou H et al. (2003) Her-2/neu expression in osteosarcoma increases risk of lung metastasis and can be associated with gene amplification. J Pediatr Hematol Oncol 25:27–32

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Medical Oncology Unit, The Churchill Hospital, Cancer Research UK, Oxford, OX3 7LJ, UK

    Srinivasan Madhusudan (Specialist Registrar)

  2. Cancer Institute and Institute of Molecular Medicine, Amrita Institute of Medical Sciences, Elamakkara P.O. Kochi, Kerala, 682026, India

    Trivadi S. Ganesan MA (Oxon), MD, MNAMS, PhD (London), FRCP (Professor, Chairman)

Authors
  1. Srinivasan Madhusudan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Trivadi S. Ganesan MA (Oxon), MD, MNAMS, PhD (London), FRCP
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Georg-Speyer-Haus, Institute for Biomedical Research, Paul-Ehrlich-Str. 42-44, 60596, Frankfurt am Main, Germany

    Bernd Groner (Director) (Director)

Rights and permissions

Reprints and permissions

Copyright information

© 2007 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Madhusudan, S., Ganesan, T.S. (2007). Tyrosine Kinase Inhibitors and Cancer Therapy. In: Groner, B. (eds) Targeted Interference with Signal Transduction Events. Resent Results in Cancer Research, vol 172. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-31209-3_3

Download citation

  • DOI: https://doi.org/10.1007/978-3-540-31209-3_3

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-31208-6

  • Online ISBN: 978-3-540-31209-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation