292
Views
109
CrossRef citations to date
0
Altmetric
Review

Small molecule tyrosine kinase inhibitors: clinical development of anticancer agents

&
Pages 51-64 | Published online: 02 Mar 2005

Bibliography

  • BLUME-JENSEN P, HUNTER T: Oncogenic kinase signalling. Nature (2001) 411:355–365.
  • •Comprehensive review of kinases implicated in cancer.
  • HANAHAN D, WEINBERG RA: The hallmarks of cancer. Cell (2000) 100:57–70.
  • ZWICK E, BANGE J, ULLRICH A: Receptor tyrosine kinases as targets for anticancer drugs. Trends MM. Med. (2002) 8:17–23.
  • SCHLESSINGERJ, ULLRICH A: Growth factor signaling by receptor tyrosine kinases. Neuron (1992) 9:383–391.
  • •Comprehensive review of RTK signalling.
  • HILGER RA, KREDTKE S, HEDLEY D et al.: Inhibition of ERK phosphorylation and clinical outcome in patients treated with the Raf kinase inhibitor BAY 43–9006. Proc. Am. Soc. Clin. Oncol (2002) 21 (Abstract 1916).
  • MITCHELL DY, REID JM, PARCHMENT RE et al: Pharmacokinetics (PK) and pharmacodynamics of the oral MEK inhibitor, CI-1040, following multiple dose administration to patients with advanced cancer. Proc. Am. Soc. Clin. Oncol. (2002) 21 (Abstract 320).
  • LIOTTA LA, KOHN EC: The microenvironment of the tumour-host interface. Nature (2001) 411:375–379.
  • MAHER EA, FURNARI FB, BACHOO RIVI et al.: Malignant glioma: genetics and biology of a grave matter. Genes Dev. (2001) 15:1311–1333.
  • HEINRICH MC, BLANKE CD, DRUKER BJ, CORLESS CL: Inhibition of KIT tyrosine kinase activity: a novel molecular approach to the treatment of KIT-positive malignancies. I Clin. Oncol (2002) 20:1692–1703.
  • SHIMIZU A, O'BRIEN KP, SJOBLOM Tet al.: The dermatofibrosarcoma protuberans-associated collagen type Tali platelet-derived growth factor (PDGF) B-chain fusion gene generates a transforming protein that is processed to functional PDGF-BB. Cancer Res. (1999) 59:3719–3723.
  • MAURO MJ, O'DWYER M, HEINRICH MC, DRUKER BJ: STI-571: A paradigm of new agents for cancer therapeutics. Clin. Oncol. (2002) 20:325–334.
  • •Good review of imatinib mesylate.
  • GILLILAND DG, GRIFFIN JD: Role of FLT3 in leukemia. Curr: Opin. Hematol (2002) 9:274–281.
  • BEGHINI A, LARIZZA L, CAIROLI R, MORRA E: c-Kit activating mutations and mast cell proliferation in human leukemia. Blood(1998) 92:701–703.
  • REILLY IT: Class III receptor tyrosine kinases: role in leukaemogenesis. Br. J. Haematol. (2002) 116:744–757.
  • KLINT P, CLAESSON-WELSH L: Signal transduction by fibroblast growth factor receptors. Front. Biosci. (1999) 4:165–177.
  • GUASCH G, OLLENDORFF V, BORG J-P, BIRNBAUM D, PEBUSQUE M-J: 8p12 stem cell myeloproliferative disorder: the FOP-fibroblast growth factor receptor 1 fusion protein of the t(6,8) translocation induces cell survival mediated by mitogen-activated protein kinase and phosphatidylinositol 3-kinase/Akt/mTOR pathways. MM. Cell. Biol. (2001) 21:8129–8142.
  • POPOVICI C, ADELAIDE J, OLLENDORFF V et al.: Fibroblast growth factor receptor 1 is fused to FIM in stem-cell myeloproliferative disorder with t(8;13) (p12;q12) . Proc. Nati Acad. Sci. USA (1998) 95:5712–5717.
  • SOHAL J, CHASE A, MOULD S et al.: Identification of four new translocations involving FGFR1 in myeloid disorders. Genes Chromosomes Cancer (2001) 32:155–163.
  • OLLENDORFF V, GUASCH G, ISNARDON D et al.: Characterization of FIM-FGFR1, the fusion product of the myeloproliferative disorder-associated t(8;13) translocation. J. Biol. Chem. (1999) 274:26922–26930.
  • REITER A, SOHAL J, KULKARNI S et al: Consistent fusion of ZNF198 to the fibroblast growth factor receptor-1 in the t(8,13)(p11;q12) myeloproliferative syndrome. Blood (1998) 92: 1735-1742.
  • TOMASSON MH, WILLIAMS IR, HASSERJIAN R et al: TEL/PDGFI3R induces hematologic malignancies in mice that respond to a specific tyrosine kinase inhibitor. Blood(1999) 93: 1707-1714.
  • HIDALGO M, ERLICHMAN C, ROWINSKY EK et al: Phase I trial of EKB-569, an irreversible inhibitor of the epidermal growth factor receptor (EGFR), in patients with advanced solid tumors. Proc. Am. Soc. Clin. Oncol (2002) 21 (Abstract 65).
  • KRIS MG, NATALE RB, HERBST RS et al: A phase II trial of ZD1839 CIressa') in advanced non-small cell lung cancer (NSCLC) patients who had failed platinum-and docetaxel-based regiments (IDEAL2). Proc. Am. Soc. Clin. Oncol (2002) 21 (Abstract 1166).
  • FUKUOKA M, YANO S, GIACCONE G et al: Final results from a phase II trial of ZD1839 (Iressa') for patients with advanced non-small-cell lung cancer (IDEAL1). Proc. Am. Soc. Clin. Oncol. (2002) 21 (Abstract 1188).
  • KIES MS, ARQUETTE M, NABELL L et al.: Final report of the efficacy and safety of the anti-epidermal growth factor antibody, cetuximab (IMC-C225), in combination with cisplatin in patients with recurrent squamous cell carcinoma of the head and neck (SCCHN) refractory to cisplatin containing chemotherapy. Proc. Am. Soc. Clin. Oncol. (2002) 21 (Abstract 925).
  • CHRISTENSEN JG, SCHRECK RE, CHAN E et al.: High levels of HER-2 expression alter the ability of epidermal growth factor receptor (EGER) family tyrosine kinase inhibitors to inhibit EGFR phosphorylation in vivo. Clin. Canc. Res. (2001) 7:4230–4238.
  • ANIDO J, ALBANNEL J, ROJO F et al.: ZD1839 (Iressa'), a specific epidermal growth factor receptor (EGER) tyrosine kinase inhibitor, induces the formation of inactive EGFR/HER2 and EGFR/HER3 heterodimers and prevents heregulin signaling in HERZ overexpressing breast cancer cells. Proc. Am. Assoc. Cancer Res. (2002) 43:783.
  • HERBST RS, MADDOX AM, ROTHENBERG ML et al: Selective oral epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 is generally well-tolerated and has activity in non-small-cell lung cancer and other solid tumors: Results of a Phase I Trial. J. Clin. Oncol. (2002) 20:3815–3825.
  • ••Phase I results with ZD1839.
  • WOOD JM, BOLD G, BUCHDUNGER E et al.: 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. (2000) 60:2178–2189.
  • YUNG WKA, FRIEDMAN H, JACKSON E et al.: A phase I trial of PTK787/ZK 222584 (PTK/ZK), a novel oral VEGFR TK inhibitor in recurrent glioblastoma. Proc. Am. Soc. Clin. Oncol. (2002) 21 (Abstract 315).
  • DREVS J, SCHMIDT-GERSBACH GI,MROSS K et al.: Surrogate markers for the assessment of biological activity of the VEGF-receptor inhibitor PTK787/ZK 222584 (PTK/ZK) in two clinical phase I trials. Proc. Am. Soc. Clin. Oncol. (2002) 21 (Abstract 337).
  • THOMAS A, MORGAN B, DREVS J et al.: Pharmacodynamic results using dynamic contrast enhanced magnetic resonance imaging, of 2 Phase 1 studies of the VEGF inhibitor PTK787/ZK 222584 in patients with liver metastases from colorectal cancer. Proc. Am. Soc. Clin. Oncol. (2001) 20 (Abstract 279).
  • BERGSLAND EK, FEHRENBACHER L, NOVOTNY W et al: Bevacizumab (BV) + chemotherapy (CT) may improve survival in metastatic colorectal cancer (MCRC) subjects with unfavorable prognostic indicators. Proc. Am. Soc. Clin. Oncol. (2001) 20 (Abstract 2247).
  • YANG JC, HAWORTH L, STEINBERG SM, ROSENBERG SA, NOVOTNY W: A randomized double-blind placebo-controlled trial of bevacizumab (anti-VEGF antibody) demonstrating a prolongation in time to progression in patients with metastatic renal cancer. Proc. Am. Soc. Clin. Oncol. (2002) 21 (Abstract 15).
  • MENDEL DB, LAIRD AD, XIN X et al: Development of a preclinical pharmacokinetic/pharmacodynamic relationship for the angiogenesis inhibitor SU11248, a selective inhibitor of VEGF and PDGF receptor tyrosine kinases in clinical development. Proc. Am. Soc. Clin. Oncol. (2002) 21 (Abstract 94).
  • MENDEL DB, LAIRD AD, XIN X et al: In vivo anti-tumor activity of SU11248, a novel tyrosine kinase inhibitor targeting VEGF and PDGF receptors: determination of a pharmacokinetic/pharmacodynamic relationship. Clin. Canc. Res. (In press).
  • ••Determination of the predinicalpharmacokinetic/pharmacodynamic relationship for SU11248.
  • ROBERTS WG, JANI J, BEEBE J et al.: Preclinical development of CP-547,632, a novel VEGFR-2 inhibitor for cancer therapy. Proc. Am. Soc. Gin. Oncol. (2002) 21 (Abstract 473).
  • HU-LOWE D, HALLIN M, FEELEY R et al.: Characterization of potency and activity of the VEGF/PDGF receptor tyrosine kinase inhibitor AG013736. Proc. Am. Assoc. Cancer Res. (2002) 43:1082.
  • HU-LOWE D, HELLER D, BREKKEN J et al.: Pharmacological activities of AG013736, a small molecule inhibitor of VEGF/PDGR receptor tyrosine kinase. Proc. Am. Assoc. Cancer Res. (2002) 43:1082.
  • ABRAMS TJ, LEE LB, MURRAY LJ, MENDEL DB, CHERRINGTON JM: Inhibition of Kit-positive SCLC growth by SU11248, a novel tyrosine kinase inhibitor. Proc. Am. Assoc. Cancer Res. (2002) 43:337.
  • SEBTI SM, HAMILTON AD: Design of growth factor antagonists with antiangiogenic and antitumor properties. Oncogene (2000) 19:6566–6573.
  • FERRARA N: VEGF: an update on biological and therapeutic aspects. Curr. Opin. Biotech. (2000) 11:617–624.
  • LINDAHL P, JOHANSSON BR, LEVEEN P, BETSHOLTZ C: Pericyte loss and microaneurysm formation in PDGF-B-deficient mice. Science (1997) 277:242–245.
  • CHERRINGTON JM, STRAWN LM, SHAWVER LK: New paradigms for the treatment of cancer; the role of anti-angiogenesis agents. In: Advances in Cancer Research. G Klein, GF van de Woude (Eds), Academic Press, San Diego, CA, USA (2000):1–38.
  • LAIRD AD, CHRISTENSEN JG, LI G et al: 5U6668 inhibits Flk-1/KDR and PDGFRI3 in vivo, resulting in rapid apoptosis of tumor vasculature and tumor regression in mice. FASEB (2002) 16:681–690.
  • COHEN MH, WILLIAMS G, JOHNSON JR et al.: Approval summary for imatinib mesylate capsules in the treatment of chronic myelogenous leukemia. Gin. Cancer Res. (2002) 8:935–942.
  • ••FDA approval summary for imatinibmesylate in CML.
  • DAGHER R, COHEN M, WILLIAMS G et al.: Approval summary: imatinib mesylate in the treatment of metastatic and/or resectable malignant gastrointestinal stromal tumors. Clin. Cancer Res. (2002) 8:3034–3038.
  • ••FDA approval summary for imatinibmesylate in GIST.
  • APPERLEY JF, GARDEMBAS M, MELO JV et al.: Response to Imatinib Mesylate in patients with chronic myeloproliferative diseases with rearrangements of the platelet-derived growth factor receptor 13. N Engl. J. Med. (2002) 347:481–487.
  • ••Dramatic responses to imatinib mesylatedocumented in several patients with activating mutations of PDGFR-13.
  • RUBIN BP, SCHUETZE SM, EARY JF et al.: Molecular targeting of platelet-derived growth factor B by Imatinib Mesylate in a patient with metastatic Dermatofibrosarcoma protuberans. Clin. Oncol. (2002) 20:3586–3591.
  • MAKI RG, AWAN RA, DIXON RH, JHANWAR S, ANTONESCU CR: Differential sensitivity to imatinib of 2 patients with metastatic sarcoma arising from Dermatofibrosarcoma protuberans. Int. Cancer (2002) 100:623–626.
  • JOHNSON BE, FISHER B, FISHER T et al.: Phase II study of 5T15 71 (GleevecTM) for patients with small cell lung cancer. Proc. Am. Soc. Clin. Oncol. (2002) 21 (Abstract 1171).
  • HADDAD R, LIPSON KE, WEBB CP: Hepatocyte growth factor expression in human cancer and therapy with specific inhibitors. Anticancer Res. (2001) 21:4243–4252.
  • DANILKOVITCH-MIAGKOVA A, ZBAR B: Dysregulation of Met receptor tyrosine kinase activity in invasive tumors.' Clin. Invest. (2002) 109:863–867.
  • HOLASH J, WIEGAND SJ, YANCOPOULOS GD: New model of tumor angiogenesis: dynamic balance between vessel regression and growth mediated by angiopoietins and VEGF. Oncogene (1999) 18:5356–5362.
  • ARNOLD LD, DIXON R, TALANIAN R et al.: Molecular interactions in crystal structures of potent inhibitors bound to the kinase domain of Tie-2. Proc. Am. Assoc. Cancer Res. (2002) 43:848.
  • WISHART N, ARNOLD LD, BARLOZZARI T et al.: Structure activity relationships for a novel series of pyrrolo[2,3-d]pyrimidine Tie-2 inhibitors. Proc. Am. Assoc. Cancer Res. (2002) 43:848.
  • QIAN X-D, GEORGE JS, MOSKEY MD et al.: Inhibition of angiogenesis by BSF 466895 (A-422885.66), a potent and selective low molecular weight Tie-2 kinase inhibitor. Proc. Am. Assoc. Cancer Res. (2002) 43:1080.
  • THURSTON G, RUDGE JS, IOFFE E et al.: Angiopoietin-1 protects the adult vasculature against plasma leakage. Nat. Med. (2000) 6:460–463.
  • IRBY RB, YEATMAN TJ: Role of Src expression and activation in human cancers. Oncogene (2000) 19:5636–5642.
  • BISCARDI JS, TICE DA, PARSONS SJ: c-Src, receptor tyrosine kinases, and human cancer. Adv. Cancer Res. (1999) 76:61–119.
  • BELSCHES-JABLONSKI AP, BISCARDI JS, PEAVY DR et al.: Src family kinases and HERZ interactions in human breast cancer cell growth and survival. Oncogene (2001) 20:1465–1475.
  • ALLGAYER H, BOYD DD, HEISS MM et al.: Activation of Src kinase in primary colorectal carcinoma. An indicator of poor clinical prognosis. Cancer (2002) 94:344–351.
  • KANE LP, LIN J, WEISS A: Signal transduction by the TCR for antigen. Curr. Opin. Immunol. (2000) 12:242–249.
  • BLAKE RA, BROOME MA, LIU X et al.: 5U6656, a selective src family kinase inhibitor, used to probe growth factor signaling. Mol. Cell. Biol. (2000) 20:9019–9027.
  • MISSBACH M, JESCHKE M, FEYEN J et al.: A novel inhibitor of the tyrosine kinase Src suppresses phosphorylation of its major cellular substrates and reduces bone resorption in vitro and in rodent models in vivo. Bone (1999) 24:437–449.
  • SHAKESPEARE W, YANG M, BOHACEK R et al.: Structure-based design of an osteoclast-selective, nonpeptide src homology 2 inhibitor with in vivo antiresorptive activity. Proc. Nati Acad. Sci. USA (2000) 97:9373–9378.
  • VIOLETTE SM, GUAN W, BARTLETT C et al.: Bone-targeted Src 5H2 inhibitors block Src cellular activity and osteoclast-mediated resorption. Bone (2001) 28:54–64.
  • IRBY RB, MAO W, COPPOLA D et al.: Activating SRC mutation in a subset of advanced human colon cancers. Nat. Genet. (1999) 21:187–190.
  • REIFENBERGER G, ICHIMURA K, REIFENBERGER J et al.: Refined mapping of 12q13-q15 amplicons in human malignant gliomas suggests CDK4/SAS and MDM2 as independent amplification targets. Cancer Res. (1996) 56:5141–5145.
  • GAFFEY MJ, FRIERSON HF Jr, WILLIAMS ME: Chromosome 11q13, c-erbB-2, and c-myc amplification in invasive breast carcinoma: clinicopathologic correlations. Modern Pathology (1993) 6:654–659.
  • REITER RE, SATO I, THOMAS G et al.: Coamplification of prostate stem cell antigen (PSCA) and MYC in locally advanced prostate cancer. Genes Chromosomes Cancer (2000) 27:95–103.
  • PEGRAM MD, PAULETTI G, SLAMON DJ: HER-2/neu as a predictive marker of response to breast cancer therapy. Breast Cancer Res. Treat. (1998) 52:65–77.
  • DAVIES H, BIGNELL GR, COX C et al.: Mutations of the BRAF gene in human cancer. Nature (2002) 417:949–954.
  • MACDONALD TJ, BROWN KM, LAFLEUR B et al.: Expression profiling of medulloblastomas: PDGFRA and the RAS/ MAPK pathway as therapeutic targets for metastatic disease. Nat. Genet. (2001) 29:143–152.
  • •Identification of a primary tumour transcript expression fingerprint' diagnostic for metastatic medulloblastoma.
  • PETRICOIN EF, ARDEKANI AM, HITT BA et al.: Use of proteomic patterns in serum to identify ovarian cancer. Lancet (2002) 359:572–577.
  • •Identification of a serum proteomic fingerprint' diagnostic for ovarian cancer.
  • ALBANELL J, ROJO F, AVERBUCH S et al.: Pharmacodynamic studies of the epidermal growth factor receptor inhibitor ZD1839 in skin from cancer patients: Histopathologic and molecular consequences of receptor inhibition.' Clin. Oncol. (2002) 20:110–124.
  • ••Pioneering biomarker study for ZD1839in surrogate tissue (skin).
  • HU-LOWE D, HELLER D, BREKKEN J et al.: Pharmacological activities of AG013736, a small molecule inhibitor of VEGF/PDGF receptor tyrosine kinases. Proc. Am. Assoc. Cancer Res. (2002).
  • MENDEL DB, LAIRD DA, SMOLICH B et al.: Development of 5U5416, a Selective Small Molecule Inhibitor of VEGF Receptor Tyrosine Kinase Activity, as an Anti-Angiogenesis Agent. Anti-Cancer Drug Design (2000) 15:29–41.
  • STOPECK A, SHELDON M, VAHEDIAN M et al.: Results of a Phase I Dose-escalating Study of the Antiangiogenic Agent, 5U5416, in Patients with Advanced Malignancies. Clin. Cancer Res. (2002) 8:2798–2805.
  • ARTEAGA CL, JOHNSON DH: Tyrosine kinase inhibitors-ZD1839 (Iressa). Carr. Opin. Oncol. (2001) 13:491–498.
  • KIES MS, ARQUETTE M, NABELL L et al.: Final report of the efficacy and safety of the anti-epidermal growth factor antibody, cetuximab (IMC-C225), in combination with cisplatin in patients with recurrent squamous cell carcinoma of the head and neck (SCCHN) refractory to cisplatin containing chemotherapy. Proc. Am. Soc. Clin. Oncology(2002) 21:232a (Abstract 925).
  • STRUMBERG D, BAUER RJ, MOELLERJG et al.: Final results of a phase I pharmacokinetic and pharmacodynamic study of the raf kinase inhibitor BAY 43–9006 in patients with solid tumors. Proc. Am. Soc. Clin. Oncol (2002) 21 (Abstract 121).
  • MOORE M, HIRTE H, OZA A et al: Phase I study of the Raf-1 kinase inhibitor BAY 43–9006 in patients with advanced refractory solid tumors. Proc. Am. Soc. Clin. Omni (2002) 21 (Abstract 1816).
  • LORUSSO P, ADJEI AA, MEYER MB et al.: A phase I clinical and pharmacokinetic evaluation of the oral MEK inhibitor, CI-1040, administered for 21 consecutive days, repeated every 4 weeks in patients with advanced cancer. Proc. Am. Soc. Clin. Oncol (2002) 21 (Abstract 321).
  • GORDON MS, MARGOLIN K, TALPAZ M et al.: Phase I safety and pharmacokinetic study of recombinant human anti-vascular endothelial growth factor in patients with advanced cancer. Clin. Oncol (2001) 19:843–850.
  • LI B, OGASAWARA AK, YANG R et al.: KDR (VEGF receptor 2) is the major mediator for the hypotensive effect of VEGF. Hypertension (2002) 39:1095–1100.
  • EPPLER SM, COMBS DL, HENRY TD et al.: A target-mediated model to describe the pharmacokinetics and hemodynamic effects of recombinant human vascular endothelial growth factor in humans. Clin. Pharmacol flier: (2002) 72:20–32.
  • GORRE ME, SAWYERS CL: Molecular mechanisms of resistance to 5TI571 in chronic myeloid leukemia. Curr: Opin. Hematol (2002) 9:303–307.
  • •Incisive review of mechanisms underlying resistance to irnatinib mesylate in CML patients.
  • BLAGOSKLONNY MV: STI-571 must select for drug-resistant cells but no cell breathes fire out of its nostrils like a dragon'. Leukemia (2002) 16:570–572.
  • GORRE ME, MOHAMMED M, ELLWOOD K et al.: Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science (2001) 293:876–880.
  • ROCHE-LESTIENNE C, SOENEN-CORNU V, GRARDEL-DUFLOS N et al: Several types of mutations of the Abl gene can be found in chronic myeloid leukemia patients resistant to STI571, and they can pre-exist to the onset of treatment. Blood (2002) 100:1014–1018.
  • GALE NW, YANCOPOULOS GD: Growth factors acting via endothelial cell-specific receptor tyrosine kinases: VEGFs, angiopoietins, and ephrins in vascular development. Genes Dev. (1999) 13:1055–1066.
  • LUTTUN A, TJVVA M, MOONS Let al.: Revascularization of ischemic tissues by P1GF treatment, and inhibition of tumor angiogenesis, arthritis and atherosclerosis by anti-Fltl. Nat. Med. (2002) 8:831–840.
  • AGUAYO A, MANSHOURI T, O'BRIEN S et al.: Clinical relevance of Flt1 and Tie], angiogenesis receptors expression in B-cell chronic lymphocytic leukemia (CLL). Leukemia Res. (2001) 25:279–285.
  • FERRAJOLI A, MANSHOURI T, ESTROV Z et al.: High levels of vascular endothelial growth factor receptor-2 correlate with shortened survival in chronic lymphocytic leukemia. Clin. Canc. Res. (2001) 7:795–799.
  • FOSS B, ULVESTAD E, BRUSERUD 0: Platelet-derived growth factor (PDGF) in human acute myelogenous leukemia: PDGF receptor expression, endogenous PDGF release and responsiveness to exogenous PDGF isoforms by in vitro cultured acute myelogenous leukemia blasts. Eur. Haematol (2001) 67:267–278.
  • BENJAMIN LE, HEMO I, KESHET E: A plasticity window for blood vessel remodelling is defined by pericyte coverage of the preformed endothelial network and is regulated by PDGF- B and VEGE Development (1998) 125:1591–1598.
  • CHESI M, NARDINI E, LIM RSC et al.: The t(4,14) translocation in myeloma dysregulates both FGFR3 and a novel gene, MMSET, resulting in IgH/MMSET hybrid transcripts. Blood (1998) 92:3025–3034.
  • CHESI M, BERGSAGEL PL, KUEHL WM: The enigma of ectopic expression of FGFR3 in multiple myeloma: a critical initiating event or just a target for mutational activation during tumor progression. Curr: Opin. Hematol (2002) 9:288–293.
  • CHESI M, NARDINI E, BRENTS LA et al.: Frequent translocation t(4,14)(p16.3;q32.3) in multiple myeloma is associated with increased expression and activating mutations of fibroblast growth factor receptor 3. Nat. Genet. (1997) 16:260.
  • LIZ, ZHU YX, PLOWRIGHT EE et al: The myeloma-associated oncogene fibroblast growth factor receptor 3 is transforming in hematopoietic cells. Blood (2001) 97:2413–2419.
  • WAKELING AE, GUY SP, WOODBURN JR et al: ZD1839 (Iressa): An Orally Active Inhibitor of Epidermal Growth Factor Signaling with Potential for Cancer Therapy. Cancer Res. (2002) 62:5749–5754.
  • RATAIN MJ, GEORGE CM, JANISCH L et al.: Phase I trial of erlotinib (OSI-774) in combination with gemcitabine (G) and cisplatin (P) in patients with advanced solid tumors. Proc. Am. Soc. Clin. Oncol (2002) 21 (Abstract 2115).
  • FORERO L, PATNAIK A, HAMMOND LA et al.: Phase I, pharmacokinetic (PK) and biologic study of OSI-774, a selective epidermal growth factor (EGER) tyrosine kinase (TK) inhibitor in combination with paclitaxel and carboplatin. Proc. Am. Soc. Clin. Oncol (2002) 21 (Abstract 1908).
  • FOROUZESH B, HIDALGO M, TAKIMOTO C et al.: Phase I, pharmacokinetic (PK), and biological studies of the epidermal growth factor-tyrosine kinase (EGFR-TK) inhibitor OSI-774 in combination with docetaxel. Proc. Am. Soc. Clin. Omni (2002) 21 (Abstract 81).
  • ROGERS LR, KAELINE W, NADLER P, SHIELDS AF, LORUSSO P: Response of cerebellar hemangioblastomas associated with von Hippel-Lindau disease to OSI-774 (Tarceval . Proc. Am. Soc. Clin. Oncol (2002) 21 (Abstract 2111).
  • RINEHART JJ, WILDING G, WILLSON J et al.: A phase I clinical and pharmacokinetic study of oral CI-1033, a pan-erbB tyrosine kinase inhibitor, in patients with advanced solid tumors. Proc. Am. Soc. Clin. Omni (2002) 21 (Abstract 41).
  • ZINNER RG, DONATO NJ, NEMUNAITIS JJ et al: Biomarker modulation in tumor and skin biopsy samples from patients with solid tumors following treatment with the pan-erbB tyrosine kinase inhibitor, CI-1033. Proc. Am. Soc. Clin. Omni (2002) 21 (Abstract 58).
  • OLSON SC, BAKER L, CUNNINGHAM CC et al.: A population pharmacokinetic (PPK) analysis of oral CI-1033, a pan-erbB tyrosine kinase inhibitor, in patients with advanced solid tumors. Proc. Am. Soc. Clin. Oncol (2002) 21 (Abstract 361).
  • HOEKSTRA R, DUMEZ H, VAN OOSTEROM AT et al.: A phase I and pharmacological study of PKI166, an epidermal growth factor receptor (EGER) tyrosine kinase inhibitor, administered orally in a two weeks on, two weeks off scheme to patients with advanced cancer. Proc. Am. Soc. Clin. Oncol. (2002) 21 (Abstract 340).
  • DUMEZ H, HOEKSTRA R, ESKENS F et al.: A phase I and pharmacological study of PKI166, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, administered orally 3 times a week to patients with advanced cancer. Proc. Am. Soc. Clin. Oncol. (2002) 21 (Abstract 341).
  • XIA W, MULLIN RJ, KEITH BR et at Anti-tumor activity of GW572016: a dual tyrosine kinase inhibitor blocks EGF activation of EGFR/erbB2 and downstream Erk1/2 and AKT pathways. Oncogene (2002) 21:6255–6263.
  • DeSIMONE PA, BENCE AK, ANDERSON EB et al.: A phase I study to investigate the safety, tolerability and pharmacokinetics of single oral escalating doses of GW572016 in healthy volunteers. Proc. Am. Soc. Clin. Oncol. (2002) 21 (Abstract 375).
  • HURWITZ H, HOLDEN SN, ECKHARDT SG et al.: Clinical evaluation of ZD6474, an orally active inhibitor of VEGF signaling, in patients with solid tumors. Proc. AM. Soc. Clin. Oncol. (2002) 21 (Abstract 383).
  • VON MEHREN M, BLANKE C, JOENSUU H et al.: High incidence of durable responses induced by imatinib mesylate (Gleevec) in patients with unresectable and metastatic gastrointestinal stromal tumors (GIST). Proc. Am. Soc. Clin. Oncol. (2002) 21 (Abstract 1608).
  • HEINRICH MC, CORLESS CL, BLANKE C et al.: KIT mutational status predicts clinical response to 5TI571 in patients with metastatic gastrointestinal stromal tumors (GISTs). Proc. Am. Soc. Clin. Oncol. (2002) 21 (Abstract 6).
  • VAN DEN ABBEELE AD, BADAWI RD, CLICHE J-P et al.: 18F-FDG-PET predicts response to imatinib mesylate (Gleevec) in patients with advanced gastrointestinal stromal tumors (GIST). Proc. Am. Soc. Clin. Oncol. (2002) 21 (Abstract 1610).
  • LAIRD AD, VAJKOCZY P, SHAWVER LK et al.: 5U6668 is a potent antiangiogenic and antitumor agent that induces regression of established tumors. Cancer Res. (2000) 60:4152–4160.
  • BRITTEN CD, ROSEN LS, KABBINAVAR F et al.: Phase I trial of 5U6668, a small molecule receptor tyrosine kinase inhibitor, given twice daily in patients with advanced cancers. Proc. Am. Soc. Clin. Oncol. (2002) 21 (Abstract 1922).
  • WEISBERG E, BOULTON C, LOUISE K et al.: Inhibition of mutant FLT3 receptors in leukemia cells by a small molecule tyrosine kinase inhibitor. Proc. Am. Soc. Clin. Oncol. (2002) 21 (Abstract 16).
  • FABBRO D, RUETZ S, BODIS S et PKC412 - a protein kinase inhibitor with a broad therapeutic potential. Anti-cancer Drug Des. (2000) 15:17–28.
  • TOLCHER AW, O'LEARY JJ, DEBONO JS et al.: A phase land biologic correlative study of an oral vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitor, CP-547,632, in patients (pts) with advanced solid tumors. Proc. Am. Soc. Clin. Oncol. (2002) 21 (Abstract 16).
  • GEORGE DJ, DIONNE CA, JANI J et Sustained in vivo regression of Dunning H rat prostate cancers treated with combinations of androgen ablation and Trk tyrosine kinase inhibitors, CEP-751 (KT-6587) or CEP-701 (KT-5555). Cancer Res. (1999) 59:2395–2401.
  • LEVIS M, ALLEBACH J, TSE K-F et al.: A Flt3-targeted tyrosine kinase inhibitor is cytotoxic to leukemia cells M vitro and in vivo. Blood (2002) 99:3885–3891.
  • RUGGERI B, SINGH J, HUDKINS R et al.: CEP-7055: An orally-active VEGF-R kinase inhibitor with potent anti-angiogenic activity and anti-tumor efficacy against human tumor xenograft growth. Proc. Am. Assoc. Cancer Res. (2002) 43:1080.
  • JONES-BOLIN S, HUNTER K, ZHAO H, RUGGERI B: The effects of the orally-active VEGF-R kinase inhibitor, CEP-7055, on primary tumor growth and metastatic profile in orthotopic models of human pancreatic ductal carcinoma and murine renal carcinoma (RENCA) in mice. Proc. Am. Assoc. Cancer Res. (2002) 43:524.
  • YU J, APATIRA M, LI J et at CT53518, a specific Flt3 kinase inhibitor selectively blocks mitogenic and survival signaling pathways and induces apoptosis in human AML cells that harbor a Flt3/ITD mutation. Proc. Am. Assoc. Cancer Res. (2002) 43 (Abstract LB27).

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.