Tyrosine kinases as targets in cancer therapy – successes and failures

Bibliography

• FURETP, CARAVATTI G, LYDON N et al.: Modelling study of protein kinase inhibitors: binding mode of staurosporine and origin of the selectivity of CGP 52411. Comput. Aided Mot. Des. (1995) 9:465–472.
   PubMedGoogle Scholar
• ••First description of a pharmacophoremodel of the ATP-binding site for tyrosine kinase inhibitors.
   Google Scholar
• TRUMPP-KALLMEYER S, RUBIN JR, HUMBLET C, HAMBY JM, SHOWALTER HDH: Development of a binding model to protein tyrosine kinases for substituted pyrido [2,3-cllpyrimidine inhibitors. j Med. Chem. (1998) 41:1752–1763.
   PubMed Web of Science ®Google Scholar
• TRAXLER E FURET P: Strategies toward the design of novel and selective protein tyrosine kinase inhibitors. Pharmacol. Ther. (1999) 82:195–206.
   PubMedGoogle Scholar
• PALMER BD, TRUMPP-KALLMEYER S, FRY DW, NELSON JM, SHOWALTER HDH, DENNY WA: Tyrosine kinase inhibitors. 11. Soluble analogs of pyrrolo- and pyrazoloquinazolines as epidermal growth factor receptor inhibitors: synthesis, biological evaluation, and modelling of the mode of binding. Med. Chem. (1997) 40:1519–1529.
   Google Scholar
• TRAXLER P: Tyrosine kinase inhibitors in cancer treatment (Part II). Expert Opin. Ther. Pat. (1998) 8:1599–1625.
   Web of Science ®Google Scholar
• •Complete overview of the literature and patents prior to 1998.
   Google Scholar
• BRIDGES AJ: Current progress towards the development of tyrosine kinase inhibitors as anticancer agents. In: Emerging Drugs: The Prospect for Improved Medicines. Ashley Publications Ltd, London, UK (1998):279–292.
   Google Scholar
• TRAXLER P, BOLD G, BUCHDUNGER E et al.: Tyrosine kinase inhibitors: from rational design to clinical trials. Med. Res. Rev (2001) 21:499–512.
   PubMed Web of Science ®Google Scholar
• •Update on Novartis kinase inhibitors (STI571, PKI166, PTK7878/ZK222584).
   Google Scholar
• GARCIA-ECHEVERRIA C, TRAXLER P, EVANS DB: ATP site-directed competitive and irreversible inhibitors of protein kinases. Med. Res. Rev (2000) 20:28–57.
   PubMed Web of Science ®Google Scholar
• RENHOWE PA: Inhibitors of growth factor receptor kinase-dependent signaling pathways in anticancer chemotherapy — clinical progress. Curt: Opin. Drug Discov. Devel. (2002) 5:214–224.
   PubMedGoogle Scholar
• •• Thorough overview of EGFR tyrosine kinase inhibitors.
   Google Scholar
• FABBRO D, RUETZ S, BUCHDUNGER E etal.: Protein kinases as targets for anticancer agents: from inhibitors to useful drugs. Pharmacol Ther. (2002) 93:79–98.
   Google Scholar
• DUMAS J: Growth factor receptor kinase inhibitors: recent progress and clinical impact. Cun: Opin. Drug Discov. Dev. (2001) 4:378–389.
   PubMedGoogle Scholar
• SHAWVER L, SLAMON D, ULLRICH A: Smart drugs: tyrosine kinase inhibitors in cancer therapy. Cancer Cell (2002) 1:117–123.
   PubMed Web of Science ®Google Scholar
• MOYER JD, BARBACCI EG, IWATA KK et al.: Induction of apoptosis and cell cycle arrest by CP-358774, an inhibitor of epidermal growth factor receptor tyrosine kinase. Cancer Res. (1997) 57:4838–4848.
   PubMed Web of Science ®Google Scholar
• WOODBURN JR, BARKER AJ, GIBSON KH, ASHTON SE, WAKELING AE: ZD1839, an epidermal growth factor tyrosine kinase inhibitor selected for clinical development. Proc. Am. Assoc. Cancer Res. (1997) 38:6333.
   Google Scholar
• BRIDGES AJ: The rationale and strategy used to develop a series of highly potent, irreversible, inhibitors of the epidermal growth factor receptor family of tyrosine kinases. Curr. Med. Chem. (1999) 6:825–843.
   PubMed Web of Science ®Google Scholar
• TRAXLER PM, FURET E METT H, BUCHDUNGER E, MEYER T, LYDON N: 4-(Phenylamino) pyrrolopyrimidines: potent and selective, ATP site directed inhibitors of the EGF-receptor protein tyrosine kinase. J Med. Chem. (1996) 39:2285–2292.
   PubMed Web of Science ®Google Scholar
• ZIMMERMANN J, BUCHDUNGER E, METT H, MEYER T, LYDON NB: Potent and selective inhibitors of the ABL-kinase: phenylamino-pyrimidine (PAP) derivatives. Bioorg. Med. Chem. Lett. (1997) 7:187–192.
   Web of Science ®Google Scholar
• SUN L, TRAN N, TANG F et al: Synthesis and biological evaluations of 3-substituted indolin-2-ones: a novel class of tyrosine kinase inhibitors that exhibit selectivity toward particular receptor tyrosine kinases. J Med. Chem. (1998) 41:2588–2603.
   PubMed Web of Science ®Google Scholar
• FONG TA, SHAWVER LK, SUN L et al: SU5416 is a potent and selective inhibitor of the vascular endothelial growth factor receptor (Flk-1/KDR) that inhibits tyrosine kinase catalysis, tumor vascularization, and growth of multiple tumor types. Cancer Res. (1999) 59:99–106.
   PubMed Web of Science ®Google Scholar
• •Summary of preclinical data of 5U5416.
   Google Scholar
• SALOMON DS, BRANDT R, CIARDIELLO E NORMANNO N: Epidermal growth factor-related peptides and their receptors in human malignancies. Grit. Rev arca Hematol (1995) 19:183–232.
   PubMed Web of Science ®Google Scholar
• WOODBURN JR: The epidermal growthfactor receptor and its inhibition in cancer therapy. Pharmacol Ther. (1999) 82:241–250.
   PubMed Web of Science ®Google Scholar
• GIBBS JB: Anticancer drug targets: growth factors and growth factor signaling. I OM. Invest. (2000) 105:9–13.
   Google Scholar
• MENDELSOHN J, BASELGA J: The EGF receptor family as targets for cancer therapy. Oricogerre (2000) 19:6550–6565.
   Google Scholar
• YARDEN Y: The EGFR family and its ligands in human cancer signalling mechanisms and therapeutic opportunities. Eur. J. Cancer (2001) 37:S3–S8.
   Google Scholar
• VOLDBORG BR, DAMSTRUP L, SPANG-THOMSEN M, POULSEN HS: Epidermal growth factor receptor (EGFR) and EGFR mutations, function and possible role in clinical trials. Ann. arca (1997) 8:1197–1206.
   Google Scholar
• ••Thorough review of EGFR as a target foranticancer therapy.
   Google Scholar
• HERNANDEZ-SOTOMAYOR SMT, CARPENTER G: Epidermal growth factor receptor: elements of intracellular communication. j Membr. Biol. (1992) 128:81–89.
   PubMedGoogle Scholar
• TODDERUD G, CARPENTER G: Epidermal growth factor: the receptor and its function. BioFactors (1989) 2:11–15.
   PubMedGoogle Scholar
• VELU TJ: Structure, function and transforming potential of the epidermal growth factor receptor. Mal Cell. Eric/or/Ma (1990) 70:205–216.
   Google Scholar
• SCAMBIA G, BENEDETTI-PANICI P, FERRANDINA G et al: Epidermal growth factor, estrogen and progesterone receptor expression in primary ovarian cancer: correlation with clinical outcome and response to chemotherapy. Br j Cancer (1995) 72:361–366.
   PubMedGoogle Scholar
• MOSCATELLO DK, HOLGADO-MADRUGA M, EMLET DR, MONTGOMERY RB, WONG AJ: Constitutive activation of phosphatidylinositol 3-kinase by a naturally occurring mutant epidermal growth factor receptor. j Biol. Chem. (1998) 273:200–206.
   PubMed Web of Science ®Google Scholar
• TANG CK, GONG X-QI, MOSCATELLO DK, WONG AJ, LIPPMAN ME: Epidermal growth factor receptor VIII enhances tumorgenicity in human breast cancer. Cancer Res. (2000) 60:3081–3087.
   PubMedGoogle Scholar
• MENDELSOHN J: Epidermal growth factor receptor inhibition by a monoclonal antibody as anticancer therapy. Clirr. Cancer Res. (1997) 3:2703–2707.
   PubMed Web of Science ®Google Scholar
• GOLDSTEIN NI, PREWETT M, ZUKLYS K, ROCKWELL P, MENDELSOHN J: Biological efficacy of a chimeric antibody to the epidermal growth factor receptor in a human tumor xenograft model. Clirr. Cancer Res. (1995) 1:1311–1318.
   PubMed Web of Science ®Google Scholar
• BASELGA J, PFISTER D, COOPER MRet al.: Phase I studies of anti-epidermal growth factor receptor chimeric antibody C225 alone and in combination with cisplatin. j Chia. arca (2000) 18:904–914.
   Google Scholar
• ADJEI AA: Epidermal growth factor receptor tyrosine kinase inhibitors in cancer therapy. Drugs of the Future (2001) 26:1087–1092.
   Web of Science ®Google Scholar
• •Thorough review of EGFR inhibitors.
   Google Scholar
• CIARDIELLO E TORTORA G: Anti-epidermal growth factor receptor drugs in cancer therapy. Expert Opin. Invest. Drugs (2002) 11:755–768.
   PubMedGoogle Scholar
• •Comprehensive review of drugs targeting the EGFR.
   Google Scholar
• FRY DW: Site-directed irreversible inhibitors of the erbB family of receptor tyrosine kinases as novel chemotherapeutic agents for cancer. Anticancer Drug Des. (2000) 15:3–16.
   PubMedGoogle Scholar
• NOONBERG SB, BENZ CC: Tyrosine kinase inhibitors targeted to the epidermal growth factor receptor subfamily: role as anticancer agents. Drugs (2000) 59:753–767.
   PubMed Web of Science ®Google Scholar
• BARKER AJ, GIBSON KH, GRUNDY W et al: Studies leading to the identification of ZD1839 (Iressa): an orally active, selective epidermal growth factor receptor tyrosine kinase inhibitor targeted to the treatment of cancer. Bioorg. Med. Chem. Lett. (2001) 11:1911–1914.
   PubMed Web of Science ®Google Scholar
• •Summary of preclinical data of ZD1839 (Iressa).
   Google Scholar
• HERBST RS: ZD1839: targeting the epidermal growth factor receptor in cancer therapy. Expert Opin Invest. Drugs (2002) 11:837–849.
   PubMed Web of Science ®Google Scholar
• CIARDIELLO E CAPUTO R, BIANCO R et al.: Antitumor effect and potentiation of cytotoxic drugs activity in human cancer cells by ZD1839 (Iressa), an epidermal growth factor receptor-selective tyrosine kinase inhibitor. Clin. Cancer Res. (2000) 6:2053–2063.
   Google Scholar
• CIARDIELLO F, CAPUTO R, BIANCO R et al: Inhibition of growth factor production and angiogenesis in human cancer cells by ZD1839 (Iressa), a selective epidermal growth factor receptor tyrosine kinase inhibitor. CM]. Cancer Res. (2001) 7:1459–1465.
   PubMed Web of Science ®Google Scholar
• HIRATA A, OGAWA S, KOMETANI T et al: ZD1839 (Iressa) induces antiangiogenic effects through inhibition of epidermal growth factor receptor tyrosine kinase. Cancer Res. (2002) 62:2554–2560.
   PubMed Web of Science ®Google Scholar
• MOASSER MM, BASSO A, AVERBUCH SD, ROSEN N: The tyrosine kinase inhibitor ZD1839 (Iressa') inhibits HER2-driven signaling and suppresses the growth of HER2-overexpressing tumor cells. Cancer Res. (2001) 61:7184–7188.
   PubMed Web of Science ®Google Scholar
• SIROTNAK FM, ZAKOWSKI MF, MILLER VA, SCHER HI, KRIS MG: Efficacy of cytotoxic agents against human tumor xenografts is markedly enhanced by co-administration of ZD1839 (Iressa), an inhibitor of EGFR tyrosine kinase. Clin. Cancer Res. (2000) 6:4885–4892.
   PubMed Web of Science ®Google Scholar
• WILLIAMS KJ, TELFER BA, STRATFORD IJ, WEDGE SR: ZD1839 (Iressa'), a specific oral epidermal growth factor receptor-tyrosine kinase inhibitor, potentiates radiotherapy in a human colorectal cancer xenograft model. Br. J. Cancer (2002) 86:1157–1161.
   PubMed Web of Science ®Google Scholar
• MOULDER SL, YAKES FM, MUTHUSWAMY SK, BIANCO R, SIMPSON JF, ARTEAGA CL: Epidermal growth factor receptor (HERO tyrosine kinase inhibitor ZD1839 (Iressa) inhibits HER2/neu (erbB2)-overexpressing breast cancer cells in vitro and in vivo. Cancer Res. (2001) 61:8887–8895.
   PubMed Web of Science ®Google Scholar
• NORMANNO N, CAMPIGLIO M, DE LUCA A et al: Cooperative inhibitory effect of ZD1839 (Iressa) in combination with trastuzumab (1-lerceptin) on human breast cancer cell growth. Ann. Oncol. (2002) 13:65–72.
   PubMed Web of Science ®Google Scholar
• BASELGA J, AVERBUCH SD: ZD1839 (Iressa') as an anticancer agent. Drugs (2000) 60:33–40.
   PubMed Web of Science ®Google Scholar
• RANSON M, HAMMOND A, FERRY D et al.: 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 Chia. Omni (2002) 20:2240–2250.
   Google Scholar
• •Results of Phase I studies with ZD1839 (tolerability and efficacy).
   Google Scholar
• 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. j CM]. Omni (2002) 20:110–124.
   PubMed Web of Science ®Google Scholar
• •Description of pharmacodynamic effects of ZD1839 in patients.
   Google Scholar
• BASELGA J, YANO S, GIACCONE G et al.: Initial results from a Phase II trial of ZD1839 (IRESSA) as second- and third-line monotherapy for patients with advanced non-small-cell lung cancer (IDEAL 1). I I th AACR-NCIEORTC International Conference on Molecular Targets and Cancer Therapeutics. 7–10 November, Amsterdam, NL (2001). Abstract 126.
   Google Scholar
• POLLACK VA, SAVAGE DM, BAKER DA et al.: 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. Pharmacol Exp. Ther. (1999) 291:739–748.
   PubMed Web of Science ®Google Scholar
• •Description of preclinical profile of Tarceva.
   Google Scholar
• DULLEA RG, BARBARCCI EG, MILLER PE, MOYER JD: Induction of apoptosis by CP358774, an inhibitor of epidermal growth factor receptor tyrosine kinase in combination with cisplatin. Proceedings of the 91st Annual Meeting of the American Association for Cancer Research. 1–5 April, San Francisco, USA (2000) 41:Abstract 401.
   Google Scholar
• SIU LL, HIDALGO M, NEMUNAITIS J et al.: Dose and schedule-duration escalation of the epidermal growth factor receptor tyrosine kinase inhibitor CP-358,774: a Phase I and pharmacokinetic study. 35th Annual Meeting of the American Socieo, of Clinical Oncology 15 May (1999) 18:Abstract 388.
   Google Scholar
• KARP DD, SILBERMAN S, CSUDAE R et al.: Phase I dose-escalation study of epidermal growth factor receptor tyrosine kinase inhibitor CP-358,774 in patients with advanced solid tumors. 35th Annual Meeting of the American Socieo, of Clinical Oncology 15 May (1999) 18:Abstract 388.
   Google Scholar
• •Phase I clinical data with Tarceva.
   Google Scholar
• CARAVATTI G, BRUEGGEN J, BUCHDUNGER E et al.: Pyrrolo [2, 3-d[pyrimidine and pyrazolo [3,4- dlpyrimidine derivatives as selective inhibitors of the EGF receptor tyrosine kinase. In: ACS Symposium Series (Ed 796, Anticancer Agents) (2001):231–244.
   Google Scholar
• BRUNS CJ, SOLORZANO CC, HARBISON MT et al: Blockade of the epidermal growth factor receptor signaling by a novel tyrosine kinase inhibitor leads to apoptosis of endothelial cells and therapy of human pancreatic carcinoma. Cancer Res. (2000) 60:2926–2935.
   PubMed Web of Science ®Google Scholar
• •Data of PKI166 in predinical models.
   Google Scholar
• BRANDT R, WONG AML, HYNES NE: Mammary glands reconstituted with Neu/ ErbB2 transformed HC11 cells provide a novel orthotopic tumor model for testing anti-cancer agents. Oncogene (2001) 20:5459–5465.
   PubMedGoogle Scholar
• SOLORZANO CC, BAKER CH, TSAN R et al: Optimization for the blockade of epidermal growth factor receptor signaling for therapy of human pancreatic carcinoma. CM]. Cancer Res. (2001) 7:2563–2572.
   PubMed Web of Science ®Google Scholar
• BAKER CH, SOLORZANO CC, FIDLER IJ: Blockade of vascular endothelial growth factor receptor and epidermal growth factor receptor signaling for therapy of metastatic human pancreatic cancer. Cancer Res. (2002) 62:1996–2003.
   PubMed Web of Science ®Google Scholar
• KEDAR D, BAKER CH, KILLION JJ, DINNEY CPN, FIDLER IJ: Blockade of the epidermal growth factor receptor signaling inhibits angiogenesis leading to regression of human renal cell carcinoma growing orthotopically in nude mice. CM]. Cancer Res. (2002) 8:3592–3600.
   PubMedGoogle Scholar
• KIM S-J, UEHARA H, KARASHIMA T, SHEPHERD DL, KILLION JJ, FIDLER IJ: Blockade of epidermal growth factor receptor signaling in tumor cells and tumor-associated endothelial cells for therapy of androgen-independent human prostate cancer growing in the bone of nude mice. Clin. Cancer Res. (2003) 9(3):1200–1210.
   PubMedGoogle Scholar
• BRANDT R, O'REILLY T, WOOD J, COZENS R: Combined inhibition of EGF-receptor and VEGF-receptor kinases produces profound anti-tumor efficacy against experimental cancer. Proceedings of the 93rd Annual Meeting of the American Assodation for Cancer Research. 6–10 April, San Francisco, USA (2002) 43:Abstract 5352.
   Google Scholar
• CROYLE ML, KNAUF JA, TRAXLER P, FAGIN JA: Specific inhibition of kinase activity of RET oncoproteins and of RET-induced cell growth by PM166. Proceedings of the Endocrine Socieo/s 84th Annual Meeting. June, San Francisco, USA (2002). Abstract 114.
   Google Scholar
• MURREN JR, PAPADIMITRAKOPULOU VA, SIZER KC, VAIDYANATHRAN S, RAVERA C, ABBRUZZESE JL: A Phase I dose-escalation study to evaluate the biological activity and pharmacokinetics of PKI166, a novel tyrosine kinase inhibitor, in patients with advanced cancers. Proc. Am. Soc. Cliri. Oricol (2002) 21:Abstract 377.
   Google Scholar
• HOEKSTRA R, DUMEZ H, VAN OOSTEROM AT et al.: A Phase I and pharmacological study of PKI166, an epidermal growth factor receptor tyrosine kinase inhibitor, administered orally in a two weeks on, two weeks off scheme to patients with advanced cancer. Proc. Am. Soc. Clin. Oricol (2002) 21:Abstract 340.
   Google Scholar
• RUSNAK DW, AFFLECK K, COCKERILL SG etal.: The characterization of novel, dual ErbB2/ EGFR, tyrosine kinase inhibitors: potential therapy for cancer. Cancer Res. (2001) 61:7196–7203.
   Google Scholar
• MULLIN RJ, ALLIGOOD KJ, ALLEN PP et al: Antitumor activity of GW2016 in the EGFR positive human head and neck cancer xenograft, NH5. 92nd Meeting of the American Association for Cancer Research. 24–28 March, New Orleans, USA (2001) 42:Abstract 854.
   Google Scholar
• KEITH BR, ALLEN PP, ALLIGOOD KJ et al.: Anti-tumor activity of GW2016 in the ErbB2 positive human breast cancer xenograft, BT474. 92nd Meeting of the American Association for Cancer Research. 24–28 March, New Orleans, USA (2001) 42:Abstract 803.
   Google Scholar
• EGEBLAD M, MORTENSEN OH, VAN KEMPEN LCLT, JAATTELA M: BIBX1382BS, but not AG1478 or PD 153035, inhibits the ErbB kinases at different concentrations in intact cells. Biochem. Biophys. Res. Commun. (2001) 281:25–31.
   PubMedGoogle Scholar
• DITTRICH C, GREIM G, BORNER M et al.: Phase I and pharmacokinetic study of BIBX 1382 BS, an epidermal growth factor receptor (EGFR) inhibitor, given in a continuous daily oral administration. Eur. Cancer (2002) 38:1072–1080.
   PubMed Web of Science ®Google Scholar
• FRY DW: Inhibition of the epidermal growth factor receptor family of tyrosine kinases as an approach to cancer chemotherapy: progression from reversible to irreversible inhibitors. Pharmacol Ther. (1999) 82:207–218.
   PubMed Web of Science ®Google Scholar
• SMAILL JB, REWCASTLE GW, LOO JA et al: Tyrosine kinase inhibitors. 17. Irreversible inhibitors of the epidermal growth factor receptor: 44phenylamino)quinazoline- and 4-(phenylamino)pyrido [3 2-c11 pyrimidine-6-acrylamides bearing additional solubilizing functions. J. Med. Chem. (2000) 43:1380–1397.
   Google Scholar
• •Overview on preclinical profile of CI1033.
   Google Scholar
• SLICHENMYER WJ, ELLIOTT WL, FRY DW: CI1033, a pan-erbB tyrosine kinase inhibitor. Sem:in Oricol (2001) 28:80–85.
   PubMed Web of Science ®Google Scholar
• VINCENT PW PS, ATKINSON BE, BRIDGES AJ et al: Optimal in vivo treatment schedule for the novel EGF receptor family tyrosine kinase inhibitor PD183805 correlates with inhibition of receptor tyrosine phosphorylation. 90th Annual Meeting of the American Association for Cancer Research (1999) 40:Abstract 117.
   Google Scholar
• MEDINA L, GOMEZ L, CERNA C etal.: Investigation of the effects of the tyrosine kinase inhibitor CI1033 (PD183805) against human tumor specimens taken directly from patients. Proceedings of the 91st Annual Meeting of the American Association for Cancer Research.1-5 April, San Francisco, USA (2000) 41:Abstract 483.
   Google Scholar
• GIESEG MA, DE BOCK C, FERGUSON LR, DENNY WA: Evidence for epidermal growth factor receptor-enhanced chemosensitivity in combinations of cisplatin and the new irreversible tyrosine kinase inhibitor CI-1033. Anticancer Drugs (2001) 12:683–690.
   PubMed Web of Science ®Google Scholar
• NELSON JM, FRY DW: Akt, MAPK (Erk1/2), and p38 act in concert to promote apoptosis in response to ErbB receptor family inhibition. J. Biol. Chem. (2001) 276:14842–14847.
   PubMedGoogle Scholar
• RAO GS, MURRAY S, ETHIER SP: Radiosensitization of human breast cancer cells by a novel ErbB family receptor tyrosine kinase inhibitor. Int. J. RadMt. Oricol Biol. Phys. (2000) 48:1519–1528.
   PubMed Web of Science ®Google Scholar
• ERLICHMAN C, BOERNER SA, HALLGREN CG et al: The HER tyrosine kinase inhibitor CI1033 enhances cytotoxicity of 7-ethyl- 10-hydroxycamptothecin and topotecan by inhibiting breast cancer resistance protein-mediated drug efflux. Cancer Res. (2001) 61:739–748.
   PubMed Web of Science ®Google Scholar
• SHIN DM, NEMUNAITIS J, ZINNER RG etal.: A Phase I clinical and biomarker study of CI1033, a novel pan-ErbB tyrosine kinase inhibitor in patients with solid tumors. Proc. Am. Soc. Cliri. Oricol. (2000) 20:Abstract 283.
   Google Scholar
• GARRISON MA, TOLCHER A, MCCREERY H etal.: A Phase I and pharmacokinetic study of CI1033, a pan-ErbB tyrosine kinase inhibitor, given orally on days 1, 8, and 15 every 28 days to patients with solid tumors. Proc. Am. Soc. Cliri. Oricol. (2000) 20:Abstract 283.
   Google Scholar
• GREENBERGER LM, DISCAFAMI C, WANG Y-F et al.: EKB569: a new irreversible inhibitor of epidermal growth factor receptor tyrosine kinase for the treatment of cancer. OM Cancer Res. (2000) 6\(Suppl. 388).
   Google Scholar
• TORRANCE CJ, JACKSON PE, MONTGOMERY E et al.: Combinatorial chemoprevention of intestinal neoplasia. Nat. Med. (2000) 6:1024–1028.
   PubMed Web of Science ®Google Scholar
• RABINDRAN SK, DISCAFANI CM, FLOYD MB etal.: Antitumor activity of compound 820 in xenografts: an orally active inhibitor of Her-2 receptor tyrosine kinase. Proceedings of the 93rd Annual Meeting of the American Association for Cancer Research. 6–10 April, San Francisco, USA (2002) 43:Abstract 4965.
   Google Scholar
• BARBACCI EG, BOSCOE BP, COX ED et al.: The biological and biochemical effects of CP654577, a selective erbB2 kinase inhibitor, on human breast cancer cells. Proceedings of the 93rd Annual Meeting of the American Association for Cancer Research. 6–10 April, San Francisco, USA (2002) 43:Abstract 4969.
   Google Scholar
• NAITO K, MATSUTANI E, TAMURA T etal.: TAK165, a selective inhibitor of HER2 tyrosine kinase: 1. Nature of tyrosine kinase inhibition and selective antitumor activity in vivo and in vitro. Proceedings of the 93rd Annual Meeting of the American Association for Cancer Research. 6–10 April, San Francisco, USA (2002) 43:Abstract 3897.
   Google Scholar
• FOLKMAN J: Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat. Med. (1995) 1:27–31.
   PubMed Web of Science ®Google Scholar
• PARANGI S, O'REILLY M, CHRISTOFORI G et al: Antiangiogenic therapy of transgenic mice impairs de novo tumor growth. Proc. Natl. Acad. Sci. USA (1996) 93:2002–2007.
   PubMedGoogle Scholar
• WEINSTAT-SASLOW D, STEEG PS: Angiogenesis and colonization in the tumor metastatic process: basic and applied advances. FASEB J. (1994) 8:401–407.
   PubMed Web of Science ®Google Scholar
• FOLKMAN J: The role of angiogenesis in tumor growth. Semin. Cancer Biol. (1992) 3:65–71.
   PubMedGoogle Scholar
• •• Seminal paper in the field.
   Google Scholar
• KOELCH W, MARTINY-BARON G, KIESER A, MARME D: Regulation of the expression of the VEGFNPS and its receptors: role in tumor angiogenesis. Breast Cancer Res. Treat. (1995) 36:139–155.
   PubMedGoogle Scholar
• BREIER G, RISAU W: The role of vascular endothelial growth factor in blood vessel formation. Trends Cell Biol. (1996) 6:454–456.
   PubMed Web of Science ®Google Scholar
• FERRARA N: Vascular endothelial growth factor. Trends Cardiovasc. Med. (1993) 3:244–250.
   PubMed Web of Science ®Google Scholar
• NEUFELD G, COHEN T, GENGRINOVITCH S, POLTORAK Z: Vascular endothelial growth factor (VEGF) and its receptors. FASEB J. (1999) 13:9–22.
   PubMed Web of Science ®Google Scholar
• SENGER DR, VAN DE WATER L, BROWN LF et al.: Vascular permeability factor (VPF, VEGF) in tumor biology. Cancer Metastasis Rev (1993) 12:303–324.
   PubMed Web of Science ®Google Scholar
• MATTER A: Tumor angiogenesis as a therapeutic target. Drug Discov. Today (2001) 6:1005–1024.
   PubMed Web of Science ®Google Scholar
• WOOD JM: Inhibition of vascular endothelial growth factor (VEGF) as a novel approach for cancer therapy. Medicirria (2000) 60 (Suppl. 2):41–47.
   Google Scholar
• BILODEAU MT, FRALEY ME, HARTMAN GD: Kinase insert domain-containing receptor kinase inhibitors as anti-angiogenic agents. Expert Opin. Invest. Drugs (2002) 11:737–745.
   PubMed Web of Science ®Google Scholar
• FURET E MANLEY PW: Prospects for antiangiogenic therapies based upon VEGF inhibition. ACS Symposium Series (2001) 796:282–298.
   Google Scholar
• WOOD JM, BOLD G, BUCHDUNGER E etal.: PTK787/ZK222584, 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.
   Google Scholar
• •Description of predinical profile of PTK787/ZK222584.
   Google Scholar
• XU L, YONEDA J, HERRERA C, WOOD J, KILLION JJ, FIDLER IJ: Inhibition of malignant ascites and growth of human ovarian carcinoma by oral administration of a potent inhibitor of the vascular endothelial growth factor receptor tyrosine kinases. Int. J. arca (2000) 16:445–454.
   Google Scholar
• YANO S, HERBST RS, SHINOHARA H et al.: Treatment for malignant pleural effusion of human lung adenocarcinoma by inhibition of vascular endothelial growth factor receptor tyrosine kinase phosphorylation. Clin. Cancer Res. (2000) 6:957–965.
   PubMed Web of Science ®Google Scholar
• SOLORZANO CC, BAKER CH, BRUNS CJ et al.: Inhibition of growth and metastasis of human pancreatic cancer growing in nude mice by PTK787/ ZK222584, an inhibitor of the vascular endothelial growth factor receptor tyrosine kinases. Cancer Biother. Radiopharm. (2001) 16:359–370.
   PubMed Web of Science ®Google Scholar
• DREVS J, MULLER-DRIVER R, WITTIG C et al: PTK787/ZK222584, a specific vascular endothelial growth factor-receptor tyrosine kinase inhibitor, affects the anatomy of the tumor vascular bed and the functional vascular properties as detected by dynamic enhanced magnetic resonance imaging. Cancer Res. (2002) 62:4015–4022.
   PubMed Web of Science ®Google Scholar
• DREVS J, HOFMANN I, HUGENSCHMIDT H et al.: Effects of PTK787/ZK222584, a specific inhibitor of vascular endothelial growth factor receptor tyrosine kinases, on primary tumor, metastasis, vessel density, and blood flow in a murine renal cell carcinoma model. Cancer Res. (2000) 60:4819–4824.
   PubMed Web of Science ®Google Scholar
• •Description of antiangiogenic properties of PTK787/ZK222584.
   Google Scholar
• DREVS J, SCHMIDT-GERSBACH CIM, MROSS K etal.: Surrogate markers for the assessment of biological activity of the VEGF-receptor inhibitor PTK787/ ZK222584 (PTIQZK) in two clinical trials. Proceedings of the 37th Annual Meeting of the American Society of Clinical Oncology May (2002) 21:Abstract 337.
   Google Scholar
• ••Clinical POC of pharmacodynamic effectsof PTK787/ZK222584.
   Google Scholar
• HENNEQUIN LF, STOKES ESE, THOMAS AP etal.: Novel 4-anilinoquinazolines with C-7 basic side chains: design and structure activity relationship of a series of potent, orally active, VEGF receptor tyrosine kinase inhibitors. J. Med. Chem. (2002) 45:1300–1312.
   Google Scholar
• HENNEQUIN LF, THOMAS AP JOHNSTONE C etal.: Design and structure-activity relationship of a new class of potent VEGF receptor tyrosine kinase inhibitors. J. Med. Chem. (1999) 42:5369–5389.
   Google Scholar
• •Design of KDR inhibitors of the quinazoline class (ZD6474).
   Google Scholar
• WEDGE SR, OGILVIE DJ, DUKES M et al: ZD4190: an orally active inhibitor of vascular endothelial growth factor signaling with broad-spectrum antitumor efficacy. Cancer Res. (2000) 60:970–975.
   PubMed Web of Science ®Google Scholar
• •Predinical profile of ZD6474.
   Google Scholar
• WEDGE SR, OGILVIE DJ, DUKES M et al: ZD6474 inhibits vascular endothelial growth factor signaling, angiogenesis, and tumor growth following oral administration. Cancer Res. (2002) 62:4645–4655.
   PubMed Web of Science ®Google Scholar
• WEDGE SR, OGILVIE DJ, DUKES M et al.: Pharmacological efficacy of ZD6474, a VEGF receptor tyrosine kinase inhibitor in rat. 92nd Meeting of the American Association for Cancer Research. 24–28 March, New Orleans, USA (2001) 42:Abstract 3126.
   Google Scholar
• HURWITZ HI, ECKHARDT SG, HOLDEN SN et al: A Phase I study of ZD6474, an oral VEGF receptor tyrosine kinase inhibitor, in patients with solid tumors. PTOC. AACR-NCIEORTC Clin. Cancer Res. (2001) 7:5.
   PubMedGoogle Scholar
• •Phase I data of ZD6474.
   Google Scholar
• MENDEL DB, LAIRD AD, SMOLICH BD etal.: Development of SU5416, a selective small molecule inhibitor of VEGF receptor tyrosine kinase activity, as an anti-angiogenesis agent. Anticancer Drug Des. (2000) 15:29–41.
   Google Scholar
• STOPECK A, SHELDON M, VAHEDIAN M, CROPP G, GOSALIA R, HANNAH A: 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.
   PubMed Web of Science ®Google Scholar
• LAIRD AD, VAJKOCZYP, SHAWVER LK et al: 5U6668 is a potent antiangiogenic and antitumor agent that induces regression of established tumors. Cancer Res. (2000) 60:4152–4160.
   PubMedGoogle Scholar
• LAIRD AD, CHRISTENSEN JG, LI G, CARVER J etal.: 5U6668 inhibits Flk-1/ KDR and PDGFRb in vivo, resulting in rapid apoptosis of tumor vasculature and tumor regression in mice. FASEB J. (2002) 16:681–690.
   Google Scholar
• ROSEN LS, ROSEN PJ, KABBINAVAR F et al: Phase I experience with 5U6668, a novel multiple receptor tyrosine kinase inhibitor in patients with advanced malignancies. Proc. Am. Soc. Chia. arca (2001) 20:Abstract 383.
   Google Scholar
• MENDEL DB, LAIRD AD, XIN X et al: In vivo anti-tumor and mechanism of action studies of SU11248, a potent and selective inhibitor of the VEGF and PDGF receptors. Proceedings of the 93rd Annual Meeting of the American Association for Cancer Research. 6–10 April, San Francisco, USA (2002) 43:Abstract 5349.
   Google Scholar
• LOUIE SG, XIN X, CHRISTENSEN JG, LAIRD AD et al: Determination of the pharmacokinetic and pharmacodynamic relationships in mice for SU11248, a potent and selective inhibitor of the VEGF and PDGF receptors. Proceedings of the 93rd Annual Meeting of the American Association for Cancer Research. 6–10 April, San Francisco, USA (2002) 43:Abstract 5355.
   Google Scholar
• WIEMANN M, LEE SH, WERNETTE-HAMMOND M-E etal.: Characterization of potent tyrosine kinase inhibitors that modulate angiogenesis and proliferation of selected cancer cell lines. Proceedings of the 93rd Annual Meeting of the American Association for Cancer Research. 6–10 April, San Francisco, USA (2002) 43:Abstract 4208.
   Google Scholar
• JANI JP, BEEBE JS, EMERSON E, GANT T et al: CP547,632, a novel VEGFR-2 tyrosine kinase inhibitor for cancer therapy. Proceedings of the 93rd Annual Meeting of the American Association for Cancer Research. 6–10 April, San Francisco, USA (2002) 43:Abstract 5354.
   Google Scholar
• HU-LOWE D, HALLIN M, FEELEY R et al.: Characterization of potency and activity of the VEGF/PDGF receptor tyrosine kinase inhibitor AG013736. Proceedings of the 93rd Annual Meeting of the American Association for Cancer Research. 6–10 April, San Francisco, USA (2002) 43:Abstract 5356.
   Google Scholar
• RUGGERI BA, SINGH J, HUDKINS R etal.: CEP7055, an orally-active VEGF-R kinase inhibitor with potent anti-angiogenic and anti-tumor efficacy against human tumor xenograft growth. Proceedings of the 93rd Annual Meeting of the American Association for Cancer Research. 6–10 April, San Francisco, USA (2002) 43:Abstract 5347.
   Google Scholar
• NAKAMURA K, KAMISHOHARA M, TAZUNOKI Y etal.: In vitro characterization of KRN633, a novel small molecule inhibitor of VEGF receptor tyrosine kinases. Proceedings of the 93rd Annual Meeting of the American Association for Cancer Research. 6–10 April, San Francisco, USA (2002) 43:Abstract 876.
   Google Scholar
• DALEY GQ, VAN ETTEN RA, BALTIMORE D: Induction of chronic myelogenous leukemia in mice by the P210bcr/abl gene of the Philadelphia chromosome. Science (1990) 247:824–830.
   PubMed Web of Science ®Google Scholar
• ZIMMERMANN J, BUCHDUNGER E, METT H, MEYER T, LYDON NB, TRAXLER P: (Phenylamino)pyrimidine (PAP) derivatives: a new class of potent and highly selective PDGF-receptor autophosphorylation inhibitors. Bioorg. Med. Chem. Lett. (1996)6:1221–1226.
   Web of Science ®Google Scholar
• BUCHDUNGER E, MATTER A, DRUKER B: Bcr-Abl inhibition as a modality of CML therapeutics. Biochim. Biophys. Acta (2001) 1551:M11–M18.
   Google Scholar
• CAPDEVILLE R, BUCHDUNGER E, ZIMMERMANN J, MATTER A: Glivec (STI571, imatinib), a rationally developed, targeted anticancer drug. Nat. Rev. Drug Discov. (2002) 1:493–502.
   PubMed Web of Science ®Google Scholar
• ••Excellent review on discovery, profiling andclinical evaluation of Glivec.
   Google Scholar
• DRUKER BJ, TAMURA S, BUCHDUNGER E etal.: Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nat. Med. (1996) 2:561–566.
   Google Scholar
• CARROLL M, OHNO-JONES S, TAMURA S et al: CGP 57148, a tyrosine kinase inhibitor, inhibits the growth of cells expressing BCR-ABL, TEL-ABL, and TEL-PDGFR fusion proteins. Blood (1997) 90:4947–4952.
   PubMed Web of Science ®Google Scholar
• BERAN M, CAO X, ESTROV Z, JEHA S etal.: Selective inhibition of cell proliferation and BCR-ABL phosphorylation in acute lymphoblastic leukemia cells expressing Mr 190,000 BCR-ABL protein by a tyrosine kinase inhibitor (CGP-57148). Clin. Cancer Res. (1998) 4:1661–1672.
   Google Scholar
• BUCHDUNGER E, CIOFFI CL, LAW N etal.: Abl protein-tyrosine kinase inhibitor 5TI571 inhibits in vitro signal transduction mediated by c-Kit and platelet-derived growth factor receptors. I Pharmacol Esp. Ther. (2000) 295:139–145.
   Google Scholar
• HEINRICH MC, GRIFFITH DJ, DRUKER BJ, WAIT CL, OTT KA, ZIGLER AJ: Inhibition of c-kit receptor tyrosine kinase activity by STI 571, a selective tyrosine kinase inhibitor. Blood (2000) 96:925–932.
   PubMed Web of Science ®Google Scholar
• GAMBACORTI-PASSERINI C, LE COUTRE P et al: Inhibition of the ABL kinase activity blocks the proliferation of BCR/ABL+ leukemic cells and induces apoptosis. Blood Cells Mal Dis. (1997) 23:380–394.
   PubMed Web of Science ®Google Scholar
• DAN S, NAITO M, TSURUO T: Selective induction of apoptosis in Philadelphia chromosome-positive chronic myelogenous leukemia cells by an inhibitor of BCR-ABL tyrosine kinase, CGP 57148. Cell Death Differ (1998) 5:710–715.
   PubMed Web of Science ®Google Scholar
• LE COUTRE P, MOLOGNI L, CLERIS L et al.: In vivo eradication of human BCR/ ABL-positive leukemia cells with an ABL kinase inhibitor. j Natl. Cancer Inst. (1999) 91:163–168.
   PubMed Web of Science ®Google Scholar
• DRUKER BJ, TALPAZ M, RESTA DJ et al.: Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. New Engl. Med. (2001) 344:1031–1037.
   PubMed Web of Science ®Google Scholar
• •First clinical results with Glivec in CML.
   Google Scholar
• KANTARJIAN HM, CORTES J, O'BRIEN S et al.: Imatinib mesylate (5TI571) therapy for Philadelphia chromosome-positive chronic myelogenous leukemia in blast phase. Blood (2002) 99:3547–3553.
   Google Scholar
• TALPAZ M, SILVER RT, DRUKER BJ et al.: Imatinib induces durable hematologic and cytogenetic responses in patients with accelerated phase chronic myeloid leukemia: results of a Phase II study. Blood (2002) 99:1928–1937.
   PubMed Web of Science ®Google Scholar
• SAWYERS CL, HOCHHAUS A, FELDMAN E et al: Imatinib induces hematologic and cytogenetic responses in patients with chronic myelogenous leukemia in myeloid blast crisis: results of a Phase II study. Blood (2002) 99:3530–3539.
   PubMed Web of Science ®Google Scholar
• SAVAGE DG, ANTMAN KH: Imatinib mesylate; a new oral targeted therapy. New Engl. J Med. (2002) 9:683–693.
   Google Scholar
• DRUKER BJ: STI (Glivec) as a paradigm for cancer therapy. Trends Mol. Med. (2002) 4:S14–S18.
   Google Scholar
• GORRE ME, MOHAMMED M, ELLWOOD K et al: Clinical resistance to 5TI571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science (Washington, DC) (2001) 293:876–880.
   PubMed Web of Science ®Google Scholar
• ••Description of potential mechanisms ofGlivec resistance in CML patients.
   Google Scholar
• GORRE ME, SAWYERS CL: Molecular mechanisms of resistance to 5TI571 in chronic myeloid leukemia. Curr. Opin Hematol (2002) 9:303–307.
   PubMedGoogle Scholar
• LE COUTRE P, TASSI E, VARELLA-GARCIA M et al: Induction of resistance to the Abelson inhibitor 5TI571 in human leukemic cells through gene amplification. Blood(2000) 95: 1758-1766.
   Google Scholar
• VON BUBNOFF N, SCHNELLER F, PESCHEL C, DUYSTER J: BCR-ABL gene mutations in relation to clinical resistance of Philadelphia-chromosome-positive leukaemia to STI571: a prospective study. Lancet (2002) 359:487–491.
   PubMed Web of Science ®Google Scholar
• HOCHHAUS A, KREIL S, CORBIN A et al.: Roots of clinical resistance to STI571 cancer therapy. Science (2001) 293:2163.
   PubMed Web of Science ®Google Scholar
• SCHINDLER T, BORNMANN W, PELLICENA P, MILLER WT, CLARKSON B, KURIYAN J: Structural mechanism for 5TI571 inhibition of Abelson tyrosine kinase. Science (2000) 289: 1938-1942.
   Google Scholar
• ••First crystal structure of Abl kinase and ananalogue of Glivec providing insight into resistance mechanisms.
   Google Scholar
• ZIMMERMANN J, FURET P, BUCHDUNGER E: STI571: a new treatment modality for CML? ACS Symposium Series (2001) 796:245–259.
   Google Scholar
• MANLEY P, COWAN-JACOB SW, FABBRO D etal.: Molecular interactions between Gleevec and mutant forms of c-Abl kinase. Proceedings of the 93rd Annual Meeting of the American Association for Cancer Research. 6–10 April, San Francisco, USA (2002) 43:Abstract 4196.
   Google Scholar
• 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. j Clin.Oricol. (2002) 20:1692–1703.
   PubMed Web of Science ®Google Scholar
• ••Thorough review of KIT as a target foranticancer therapy.
   Google Scholar
• JOENSUU H, ROBERTS PJ, SARLOMO-RIKALA M etal.: Effect of the tyrosine kinase inhibitor STI571 in a patient with a metastatic gastrointestinal stromal tumor. New Engl. J. Med. (2001) 344:1052–1056.
   Google Scholar
• •Clinical POC Glivec in MT-expressing GIST.
   Google Scholar
• VAN OOSTEROM AT, JUDSON I, VERWEIJ J et al.: Safety and efficacy of imatinib (5TI571) in metastatic gastrointestinal stromal tumours: a Phase I study. Lancet (2001) 358:1421–1423.
   PubMed Web of Science ®Google Scholar
• •Phase I data of Glivec in GIST patients.
   Google Scholar
• HELDIN CH, OSTMAN A, RONNSTRAND L: Signal transduction via platelet-derived growth factor receptors. Bioclurn. Biophys. Acta (1998) 1378:F79–F113.
   Web of Science ®Google Scholar
• OSTMAN A, HELDIN CH: Involvement of platelet-derived growth factor in disease: development of specific antagonists. Adv. Cancer Res. (2001) 80:1–38.
   PubMed Web of Science ®Google Scholar
• JEFFERS M, LAROCHELLE WJ, LICHENSTEIN HS: Fibroblast growth factor in cancer: therapeutic possibilities. Expert Opin. Ther. Targets (2002) 6:469–482.
   PubMedGoogle Scholar
• KORPELAINEN El, ALITALO K: Signaling angiogenesis and lymphangiogenesis. Curr. Opin. Cell Biol. (1998) 10:159–164.
   PubMed Web of Science ®Google Scholar
• MAISONPIERRE PC, GOLDFARB M, YANCOPOULOS GD, GAO G: Distinct rat genes with related profiles of expression define a TIE receptor tyrosine kinase family. Oricogerre (1993) 8:1631–1637.
   Google Scholar
• DAVIS S, ALDRICH TH, JONES PF et al: Isolation of angiopoietin-1, a ligand for the TIE2 receptor, by secretion-trap expression cloning. Cell (1996) 87:1161–1169.
   PubMed Web of Science ®Google Scholar
• ARNOLD LD, DIXON R, TALANIAN R et al.: Molecular interactions in crystal structures of potent inhibitors bound to the kinase domain of tie-2. Proceedings of the 93rd Annual Meeting of the American Association for Cancer Research. 6–10 April, San Francisco, USA (2002) 43:Abstract 4204.
   Google Scholar
• KHANDWALA HM, MCCUTCHEON IE, FLYVBJERG A, FRIEND KE: The effects of insulin-like growth factors on tumorigenesis and neoplastic growth. Endocrine Rev (2000) 21:215–244.
   PubMed Web of Science ®Google Scholar
• VAN DER VOORT R, TAHER TEL DERKSEN PWB, SPAARGAREN M, VAN DER NEUT R, PALS ST: The hepatocyte growth factor/Met pathway in development, tumorigenesis, and B-cell differentiation. Adv. Cancer Res. (2000) 79:39–90.
   PubMed Web of Science ®Google Scholar
• LONGATI P, COMOGLIO PM, BARDELLI A: Receptor tyrosine kinases as therapeutic targets: the model of the MET oncogene. Curr. Drug Targets (2001) 2:41–55.
   PubMedGoogle Scholar
• KRYSTAL GW, HINES SJ, ORGAN CP: Autocrine growth of small cell lung cancer mediated by coexpression of c-kit and stem cell factor. Cancer Res. (1996) 56:370–376.
   PubMed Web of Science ®Google Scholar
• HIROTA S, ISOZAKI K, MORIYAMA Y et al: Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science (1998) 279:577–580.
   PubMed Web of Science ®Google Scholar
• NAKAO M, YOKOTA S, IWAI T et al: Internal tandem duplication of the flt3 gene found in acute myeloid leukemia. Leukemia (1996) 10: 1911-1918.
   Google Scholar
• YAMAMOTO Y, KIYOI H, NAKANO Y et al.: Activating mutation of D835 within the activation loop of FLT3 in human hematologic malignancies. Blood (2001) 97:2434–2439.
   PubMed Web of Science ®Google Scholar
• FABBRO D, RUETZ S, BODIS S et al: PKC412 - a protein kinase inhibitor with a broad therapeutic potential. Anticancer Drug Des. (2000) 15:17–28.
   PubMedGoogle Scholar
• WEISBERG E, BOULTON C, KELLY LM et al.: Inhibition of mutant FLT3 receptors in leukemia cells by the small molecule tyrosine kinase inhibitor PKC412. Cancer Cell (2002) 1:433–443.
   PubMed Web of Science ®Google Scholar
• LEVIS M, ALLEBACH J, TSE KF et al: A FLT3-targeted tyrosine kinase inhibitor is cytotoxic to leukemia cells in vitro and in vivo. Blood (2002) 99:3885–3891.
   PubMed Web of Science ®Google Scholar
• KELLY LM, YU JC, BOULTON CL et al: CT53518, a novel selective FLT3 antagonist for the treatment of acute myelogenous leukemia (AML). Cancer Cell (2002) 1:421–432.
   PubMed Web of Science ®Google Scholar
• SCHEVING LA, STEVENSON MC, TAYLORMOORE JM, TRAXLER P, RUSSELL WE: Integral role of EGFR in HGF-mediated hepatocyte proliferation. Biochem. Biophys. Res. Comm. (2002) 290:197–203.
   PubMed Web of Science ®Google Scholar