159
Views
77
CrossRef citations to date
0
Altmetric
Review

Therapies directed at vascular endothelial growth factor

, , &
Pages 1715-1736 | Published online: 24 Feb 2005

Bibliography

  • GOSPODAROWICZ D, ABRAHAM JA, SCHILLING J: Isolation and characterization of a vascular endothelial cell mitogen produced by pituitary-derived folliculo stellate cells. Proc. Natl. Acad. Sci. USA (1989) 86:7311–7315.
  • FERRARA N, HENZEL WI: Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells. Biochem. Biophys. Res. Commun. (1989) 161:851–858.
  • SENGER DR, GALLI SJ, DVORAK AM et al.: Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science (1983) 219:983–985.
  • HOUCK KA, FERRARA N, WINER J et al: The vascular endothelial growth factor family: identification of a fourth molecular species and characterization of alternative splicing of RNA. MM. Endocrinol (1991) 5:1806–1814.
  • SOKER S, TAKASHIMA S, MIAO HQ, NEUFELD G, KLAGSBRUN M: Neuropilin-1 is expressed by endothelial and tumor cells as an isoform specific receptor for vascular endothelial growth factor. Cell(1998) 92:735745.
  • •Identification of neuropilin-1 as a co-receptor of VEGF, addressing multiple putative new functions for neuropilin and VEGE
  • AASE K, VON EULER G, LI X et al.: Vascular endothelial growth factor-I3-deficient mice display an atrial conduction defect. Circulation (2001) 104:358–364.
  • CARMELIET P, MOONS L, LUTTUN A et al.: Synergism between vascular endothelial growth factor and placental growth factor contributes to angiogenesis and plasma extravasation in pathological conditions. Nat. Med. (2001) 7(5):575–583.
  • ••Elegant studies demonstrating synergisticfunctions of VEGF and P1GF, which can be detected under pathophysiological conditions.
  • KIRKIN V, MAZITSCHEK R, KRISHNAN J et al.: Characterization of indolinones which preferentially inhibit VEGF-C- and VEGF-D-induced activation of VEGFR-3 rather than VEGFR-2. Biochem. (2001) 268:5530–5540.
  • OLOFSSON B, JELTSCH M, ERIKSSON U, ALITALO K: Current biology of VEGF-B and VEGF-C. Carr. Opin. Biotechnol (1999) 10:528–535.
  • SKOBE M, HAMBERG LM, HAWIGHORST T et al: Concurrent induction of lymphangiogenesis, angiogenesis, and macrophage recruitment by vascular endothelial growth factor-C in melanoma. Am. J. Pathol. (2001) 159:893–903.
  • ••First experimental evidence that activation of the VEGF-C/VEGFR-3 pathway leads to tumour lymphangiogenesis and metastasis.
  • MANDRIOTA SJ, JUSSILA L, JELTSCH M et al.: Vascular endothelial growth factor-C-mediated lymphangiogenesis promotes tumour metastasis. EMBO (2001) 20:672–682.
  • BARLEON B, TOTZKE F, HERZOG C et al.: Mapping of the sites for ligand binding and receptor dimerization at the extracellular domain of the vascular endothelial growth factor receptor FLT-1. J. Biol. Chem. (1997) 272:10382–10388.
  • FUH G, LI B, CROWLEY C, CUNNINGHAM B, WELLS IA: Requirements for binding and signaling of the kinase domain receptor for vascular endothelial growth factor. J. Biol. Chem. (1998) 273:11197–11204.
  • SHALABY F, ROSSANT J, YAMAGUCHI TP et al.: Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice. Nature (1995) 376:62–66.
  • •Fundamental study on the function of VEGFR-2.
  • FONG GH, ROSSANT J, GERTSENSTEIN M, BREITMAN ML: Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium. Nature (1995) 376:66–70.
  • •Fundamental study on the function of VEGFR-1.
  • HIRATSUKA S, MINOWA 0, KUNO J, NODA T, SHIBUYA M: Flt-1 lacking the tyrosine kinase domain is sufficient for normal development and angiogenesis in mice. Proc. Nati Acad. Sci.USA (1998) 95:9349–9354.
  • ••Elegant work showing a fundamental role for the extracellular domain of Flt-1 in VEGF signalling.
  • GILLE H, KOWALSKI J, YU L et al.: A repressor sequence in the juxtamembrane domain of Flt-1 (VEGFR-1) constitutively inhibits vascular endothelial growth factor-dependent phosphatidylinositol 3'-kinase activation and endothelial cell migration. EMBO (2000) 19:4064–4073.
  • LUTTUN A, TJWA M, MOONS L et al: Revascularisation of ischemic tissues by PIGF treatment, and inhibition of tumor angiogenesis, arthritis and atherosclerosis by anti-Flt 1. Nat. Med. (2002) 8:831-840.Demonstration of role of progenitor cells and Fit–1.
  • KENDALL RL, THOMAS KA: Inhibition of vascular endothelial cell growth factor activity by an endogenously encoded soluble receptor. Proc. Nati Acad. ScL USA (1993) 90:10705–10709.
  • HORNIG C, BARLEON B, AHMAD S et al.: Release and complex formation of soluble VEGFR-1 from endothelial cells and biological fluids. Lab. Invest. (2000) 80:443–454.
  • BARLEON B, SIEMEISTER G, MARTINY-BARON G et al.: Vascular endothelial growth factor up-regulates its receptor fms-like tyrosine kinase 1 (FLT-1) and a soluble variant of FLT-1 in human vascular endothelial cells. Cancer Res. (1997) 57:5421–5425.
  • ASAHARA T, MUROHARA T, SULLIVAN A et al.: Isolation of putative progenitor endothelial cells for angiogenesis. Science (1997) 275:964–967.
  • ••Initial study on circulating endothelial cellprecursors.
  • LUTTUN A, CARMELIET G, CARMELIET P: Vascular progenitors: from biology to treatment. Trends Cardiovasc Med. (2002) 12:88–96.
  • CARMELIET P, FERREIRA V, BREIER G et al.: Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature (1996) 380:435439.
  • GERBER HP, MALIK AK, SOLAR GP et al.: VEGF regulates haematopoietic stem cell survival by an internal autocrine loop mechanism. Nature (2002) 417:954–958.
  • GITAY-GOREN H, SOKER S, VLODAVSKY I, NEUFELD G: The binding of vascular endothelial growth factor to its receptors is dependent on cell surface-associated heparin-like molecules. Biol. Chem. (1992) 267:6093–6098.
  • GITAY-GOREN H, COHEN T, TESSLER S et al.: Selective binding of VEGF121 to one of the three VEGF receptors of vascular endothelial cells. Biol. Chem.(1996) 271:5519–5523.
  • WHITAKER GB, LIMBERG BJ, ROSENBAUM JS: Vascular endothelial growth factor receptor-2 and neuropilin-1 form a receptor complex that is responsible for the differential signaling potency of VEGF(165) and VEGF(121). J. Biol. Chem. (2001) 276:25520–25531.
  • MIGDAL M, HUPPERTZ B, TESSLER Set al.: Neuropilin-1 is a placenta growth factor-2 receptor. J. Biol. Chem. (1998) 273:22272–22278.
  • MAKINEN T, OLOFSSON B, KARPANEN T et al.: Differential binding of vascular endothelial growth factor B splice and proteolytic isoforms to neuropilin-1. Biol. Chem. (1999) 274:21217–21222.
  • KOLODKIN AL, LEVENGOOD DV, ROWE EG et al.: Neuropilin is a semaphorin III receptor. Cell (1997) 90:753–762.
  • HAMADA K, OIKE Y, TAKAKURA N et al.: VEGF-C signaling pathways through VEGFR-2 and VEGFR-3 in vasculoangiogenesis and hematopoiesis. Blood (2000) 96:3793–3800.
  • VEIKKOLA T, JUSSILA L, MAKINEN T et al.: Signalling via vascular endothelial growth factor receptor-3 is sufficient for lymphangiogenesis in transgenic mice. EMBO (2001) 20:1223–1231.
  • MAKINEN T, JUSSILA L, VEIKKOLA T et al.: Inhibition of lymphangiogenesis with resulting lymphedema in transgenic mice expressing soluble VEGF receptor-3. Nat. Med. (2001) 7:199–205.
  • •This paper proves the involvment of VEGFR-3 in lymphangiogenesis.
  • DORY, KESHET E: Ischemia-Driven angiogenesis. Trends Cardiovasc Med. (1997) 7:289–294.
  • CARMELIET P, JAIN RK: Angiogenesis in cancer and other diseases. Nature (2000) 407:249–257.
  • KERBEL RS: Tumor angiogenesis: past, present and the near future. Carcinogenesis (2000) 21:505–515.
  • HANAHAN D, VVEINBERG RA: The hallmarks of cancer. Cell (2000) 100:57–70.
  • BOUCK N, STELLMACH V, HSU SC: How tumors become angiogenic. Adv. Cancer Res. (1996) 69:135–174.
  • TOI M, MATSUMOTO T, BANDO H: Vascular endothelial growth factor: its prognostic, predictive, and therapeutic implications. Lancet Oncol. (2001) 2(11):667–673.
  • BROWN LF, BERSE B, JACKMAN RW et al.: Expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in adenocarcinomas of the gastrointestinal tract. Cancer Res. (1993) 53:4727–4735.
  • LINDMARK G, GERDIN B, SUNDBERG C et al.: Prognostic significance of the microvascular count in colorectal cancer. J. Clin. Oncol. (1996) 14:461–466.
  • ITAKURA J, ISHIWATA T, SHEN B et al.: Concomitant over-expression of vascular endothelial growth factor and its receptors in pancreatic cancer. Int. J. Cancer (2000) 85:27–34.
  • BROWN LF, BERSE B, JACKMAN RW et al.: Expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in breast cancer. Human Path. (1995) 26:86–91.
  • WEIDNER N, SEMPLE P, WELCH W, FOLKMAN J: Tumor angiogenesis and metastasis. Correlation in invasive breast carcinoma. N Engl. J. Med. (1991) 324:1–6.
  • •One of the first clinical studies demonstrating a correlation between angiogenesis, tumour prognosis and metastasis.
  • TANIGAWA N, AMAYA H, MATSUMURA M et al.: Extent of tumor vascularization correlates with prognosis and hematogenous metastasis in gastric carcinoma. Cancer Res. (1996) 56:2671–2676.
  • GUIDI A, ABU-JAWDEH G, BERSE B et al.: Vascular permeability factor (vascular endothelial growth factor) expression and angiogenesis in cervical neoplasia. J. Natl. Cancer Inst. (1995) 87:1237–1245.
  • SILLMAN F, BOYCE J, FRUCHTER R: The significance of atypical vessels and neovascularization in cervical neoplasias. Am. J. Obstet. Cynecol. (1981) 139:154–157.
  • BROWN LF, BERSE B, JACKMAN RW et al.: Increased expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in kidney and bladder carcinomas. Am. J. Pathol. (1993) 143:1255–1262.
  • BOCHNER BH, COTE RJ, WEIDNER N et al.: Angiogenesis in bladder cancer: relationship between microvessel density and tumor prognosis. J. Nati Cancer Inst. (1995) 87:1603–1612.
  • BIGLER SA, DEERING RE, BRAWER MK: Comparison of microscopic vascularity in benign and malignant prostatic tissue. Human Pathol. (1993) 24:220–226.
  • OLSON TA, MOHANRAJ D, CARSON LF, RAMAKRISHNAN S: Vascular permeability factor gene expression in normal and neoplastic human ovaries. Cancer Res. (1994) 54:276–280.
  • GASPARINI G, BONOLDI E, VIALE G et al.: Prognostic and predictive value of tumour angiogenesis in ovarian carcinomas. bit.j Cancer (1996) 69:205–211.
  • GUIDI AJ, ABU-JAWDEH G, TOGNAZZI K, DVORAK HF, BROWN LF: Expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in endometrial carcinoma. Cancer (1996) 78:454–460.
  • MACCHIARINI P, FONTANINI G, HARDIN MJ, SQUARTINI F, ANGELETTI CA: Relation of neovascularisation to metastasis of non-small cell lung cancer. Lancet (1992) 340:145–146.
  • PLATE KH, BREIER G, WEICH HA, RISAU W: Vascular endothelial growth factor is a potential tumor angiogenesis factor in human glioma in vivo. Nature (1992) 359:845–848.
  • LI VW, FOLKERTH RD, WATANABE H et al.: Microvessel count and cerebrospinal fluid basic fibroblast growth factor in children with brain tumors. Lancet (1994) 344:82–86.
  • BARNHILL RL, FANDREY K, LEVY MA, MIHM MC, HYMAN B: Angiogenesis and tumor progression of melanoma: quantification of vascularity in melanocytic nevi and cutaneous malignant melanoma. Lab. Invest. (1992) 67:331–337.
  • BROWN LF, TOGNAZZI K, DVORAK H, HARRIST T: Strong expression of KDR, a vascular permeability factor/vascular endothelial growth factor receptor in AIDS-associated Kaposi's sarcoma and cutaneous angiosarcoma. Jim. Pathol. (1995) 148:1065–1074.
  • GASPARINI G, WEIDNER N, MALUTA S et al.: Intratumoral microvessel density and p53 protein: correlation with metastasis in head-and neck squamous-cell carcinomas. hat. Cancer (1993) 57:739–744.
  • BERKMAN RA, MERRILL MJ, REINHOLD WC et al.: Expression of vascular permeability factor/vascular endothelial growth factor gene in central nervous system neoplasms. Clin. Invest. (1993) 91:153–159.
  • WIZIGMANN-VOOS S, BREIER G, RISAU W, PLATE KH: Up-regulation of vascular endothelial growth factor and its receptors in von Hippel-Lindau disease-associated and sporadic hemangioblastomas. Cancer Res. (1995) 55:1358–1364.
  • BELLAMY WT, RICHTER L, FRUTIGER Y, GROGAN TM: Expression of vascular endothelial growth factor and its receptors in hematopoietic malignancies. Cancer Res. (1999) 59:728–733.
  • LYDEN D, HATTORI K, DIAS S et al.: Impaired recruitment of bone -marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth. Nat. Med. (2001) 7:1194–1201.
  • ••High importance for role of progenitor cells in tumour angiogenesis.
  • FERRER FA, MILLER LJ, LINDQUIST R et al.: Expression of vascular endothelial growth factor receptors in human prostate cancer. Urology (1999) 54:567–572.
  • SOKER S, KAEFER M, JOHNSON M et al.: Vascular endothelial growth factor-mediated autocrine stimulation of prostate tumor cells coincides with progression to a malignant phenotype. Am. Pathol. (2001) 159:651–659.
  • KOLLERMANN J, HELPAP B: Expression of vascular endothelial growth factor (VEGF) and VEGF receptor Flk-1 in benign, premalignant, and malignant prostate tissue. Am. Clin. Pathol. (2001) 116:115–121.
  • BOOCOCK CA, CHARNOCK-JONES DS, SHARKEY AM et al.: Expression of vascular endothelial growth factor and its receptors fit and KDR in ovarian carcinoma. Nati Cancer Inst. (1995) 87:506–516.
  • ITAKURA J, ISHIWATA T, SHEN B, KORNMANN M, KORC M: Concomitant over-expression of vascular endothelial growth factor and its receptors in pancreatic cancer. Int. Cancer (2000) 85:27–34.
  • PRICE DJ, MIRALEM T, JIANG S, STEINBERG R, AVRAHAM H: Role of vascular endothelial growth factor in the stimulation of cellular invasion and signaling of breast cancer cells. Cell Growth Differ. (2001) 12:129–135.
  • BACHELDER RE, CRAGO A, CHUNG J et al.: Vascular endothelial growth factor is an autocrine survival factor for neuropilin-expressing breast carcinoma cells. Cancer Res. (2001) 61:5736–5740.
  • KONIG J, TOLNAY E, WIETHEGE T, MULLER K: Co-expression of vascular endothelial growth factor and its receptor fit-1 in malignant pleural mesothelioma. Respiration (2000) 67:36–40.
  • STRIZZI L, CATALANO A, VIANALE G et al.: Vascular endothelial growth factor is an autocrine growth factor in human malignant mesothelioma. Pathol. (2001) 193:468–475.
  • LACAL PM, FAILLA CM, PAGANI E et al.: Human melanoma cells secrete and respond to placenta growth factor and vascular endothelial growth factor. Invest. Dermatol (2000) 115:1000–1007.
  • DONNINI S, MACHEIN MR, PLATE KH, WEICH HA: Expression and localization of placenta growth factor and P1GF receptors in human meningiomas. Pathol. (1999) 189:66–71.
  • SAL VEN P, LYMBOUSSAKI A, HEIKKILA P, JAASKELA-SAARI H et al.: Vascular endothelial growth factors VEGF-B and VEGF-C are expressed in human tumors. Ain.J Pathol (1998) 153:103–108.
  • FIEDLER W, GRAEVEN U, ERGUN S et al.: Vascular endothelial growth factor, a possible paracrine growth factor in human acute myeloid leukemia. Blood (1997) 89:1870–1875.
  • DIAS S, HATTORI K, ZHU Z et al.: Autocrine stimulation of VEGFR-2 activates human leukemic cell growth and migration.j Clin. Invest. (2000) 106:511–521.
  • •First demonstration that an antiVEGFR-2 antibody blocks in vivo VEGF autocrine stimulation of leukaemic cells.
  • ZIEGLER BL, VALTIERI M, PORADA GA et al.: KDR receptor. A key marker defining hematopoietic stem cells. Science (1999) 285:1553–1558.
  • RATAJCZAK MZ, RATAJCZAK J, MACHALINSKI B et al.: Role of vascular endothelial growth factor (VEGF) and placenta-derived growth factor (P1GF) in regulating human haemopoietic cell growth. Br. Haeinatol. (1998) 103:969–979.
  • MIOTLA J, MACIEWICZ R, KENDREW J, FELDMANN M, PALEOLOG E: Treatment with soluble VEGF receptor reduces disease severity in murine collagen-induced arthritis. Lab. Invest. (2000) 80:1195–1205.
  • NAGASHIMA M, YOSHINO S, ISHIWATA T, ASANO G: Role of vascular endothelial growth factor in angiogenesis of rheumatoid arthritis. Rbeumatol. (1995) 22:1624–1630.
  • FAVA RA, OLSEN NJ, SPENCER-GREEN G et al.: Vascular permeability factor/endothelial growth factor (VPFNEGF): accumulation and expression in human synovial fluids and rheumatoid synovial tissue. J. Exp. Med (1994) 180:341–346.
  • KOCH AE: Angiogenesis: implications for rheumatoid arthritis. Arthritis Rheum. (1998) 41:951–962.
  • TAICHMAN NS,YOUNG S, CRUCHLEY AT, TAYLOR P, PALE OLOG E: Human neutrophils secrete vascular endothelial growth factor. J. Leak. Biol. (1997) 62:397–400.
  • FERRARA N: Vascular endothelial growthfactor: molecular and biological aspects. Carr. Top. Microbiol Immunol (1999) 237:1–30.
  • FRANK RN: Vascular endothelial growthfactor-its role in retinal vascular proliferation. N EngL Med (1994) 331:1519–1520.
  • ADAMIS AP, MILLER JW, BERNAL MT et al.: Increased vascular endothelial growth factor levels in the vitreous of eyes with proliferative diabetic retinopathy. Am. J Optharnol (1994) 118:445–450.
  • FOLKMAN J: Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat. Med. (1995) 1:27–31.
  • AIELLO LP, PIERCE EA, FOLEY ED et al.: Suppression of retinal neovascularization in vivo by inhibition of vascular endothelial growth factor (VEGF) using soluble VEGF-receptor chimeric proteins. Proc. Natl. Acad. Sci. USA (1995) 92:10457–10461.
  • •First paper showing that recombinant soluble receptors are able to inhibit VEGF activity in vivo.
  • ALON T, HEMO I, ITIN A, PE'ERJ, STONE J, KESHET E: Vascular endothelial growth factor acts as a survival factor for newly formed retinal vessels and has implications for retinopathy of prematurity. Nat. Med. (1995) 1:1024–1028.
  • NICKOLOFF BJ, MITRA RS, VARANI J,DIXIT VM, POLVERINI P: Aberrant production of interleukin-8 and thrombospondin-1 by psoriatic keratinocytes mediates angiogenesis. Am. J. Pathol (1994) 144:820–828.
  • DETMAR M, BROWN LF, CLAFFEY KP et al.: Overexpression of vascular permeability factor/vascular endothelial growth factor and it receptors in psoriasis. J. Exp. Med. (1994) 180:1141–1146.
  • DETMAR M, BROWN LF, SCHON MP et al.: Increased microvascular density and enhanced leukocyte rolling and adhesion in the skin of VEGF transgenic mice. Investig. Dermatol (1998) 111:1–6.
  • SHULMAN K, ROSEN S, TUGNAZZI K,MANSEAU EJ, BROWN LF: Expression of vascular permeability factor (VPFNEGF) is altered in many glomerular diseases. J. Am. Soc. Nephrol (1996) 7:661–666.
  • THOMAS S, VANUYSTEL J, GRUNDEN G et al.: Vascular endothelial growth factor receptors in human mesangium M vitro and in glomerular disease. Am. Soc. NephroL (2000) 11:1236–1243.
  • McDONALD DM: Angiogenesis and remodeling of airway vasculature in chronic inflammation. Am. J. Resp. Crit. Care Med. (2001) 164:39–45.
  • KNOX AJ, CORBETT L, STOCKS J, HOLLAND E, ZHU YM, PANG L: Human airway smooth muscle cells secrete vascular endothelial growth factor: up-regulation by bradykinin via a protein kinase C and prostanoid-dependent mechanism. FASEB (2001) 15:2480–2488.
  • MEYER KC, CARD ONI A, XIANG ZZ:Vascular endothelial growth factor in bronchoalveolar lavage from normal subjects and patients with diffuse parenchymal lung disease. J. Lab. Clin. Med. (2000) 135:332–338.
  • CELLETTI F, WAUGH J, AMABILE P et al.: Vascular endothelial growth factor enhances atherosclerotic plague progression. Nat. Med. (2001) 7:425–429.
  • •Report on medium importance role of VEGF in atherosclerosis.
  • ABRAMSON LP, PAHL E, HUANG L et al.: Serum vascular endothelial growth factor as a surveillance marker for cellular rejection in pediatric cardiac transplantation. Transplantation (2002) 73:153–156.
  • KIM KJ, LI B, WINER J et aL: Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth M vivo. Nature (1993) 362:841–844.
  • ••First demonstration of the pivotal role ofVEGF in tumour growth and tumour angiogenesis using an antiVEGF-neutralising mAb.
  • SCHLAEPPI J-M, WOOD J: Targeting vascular endothelial growth factor (VEGF) for anti-tumor therapy, by anti-VEGF neutralizing monoclonal antibodies or by VEGF receptor tyrosine-kinase inhibitors. Cancer Metastasis Rev (1999) 18:473–481.
  • HICKLIN DJ, WITTE L, ZHU Z et al.: Monoclonal antibody strategies to block angiogenesis. Drug Discov. Today (2001) 6:517–528.
  • STACKER SA, CAESAR C, BALDWIN ME et al.: VEGF-D promotes the metastatic spread of tumor cells via the lymphatics. Nat. Med. (2001) 7:186–191.
  • ••First demonstration that an antiVEGF-Dantibody blocks the metastatic spread through the lymphatics system.
  • KUBO H, FUJI WARA T, JUSSILA Let al.: Involvement of vascular endothelial growth factor receptor-3 in maintenance of integrity of endothelial cell lining during tumor angiogenesis. Blood (2000) 96:546–553.
  • DE VRIESE ANS, TILTON RG, ELGER M, STEPHAN CC, KRIZ W, LAMEIRE NH: Antibodies against Vascular Endothelial Growth Factor Improve Early Renal Dysfunction in Experimental Diabetes. J. Am. Soc. Nephrol (2001) 12:993-1000. Ha DANIS RP, CIULLA TA, CRISWELL M, PRATT L: Anti-angiogenic therapy of proliferative diabetic retinopathy. Expert Opin. Pharmacother: (2001) 2:395–407.
  • PRESTA LG, CHEN H, O'CONNOR SJ et al.: Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders. Cancer Res. (1997) 57:4593–4599.
  • MULLER YA, CHEN Y, CHRISTINGER HW et al.: VEGF and the Fab fragment of a humanized neutralizing antibody: crystal structure of the complex at 2.4 A resolution and mutational analysis of the interface. Structure (1998) 6:1153–1167.
  • •In-depth study of the structural elements involved in the binding of a neutralising antibody and VEGE
  • GERBER HP, KOWALSKI J, SHERMAN D, EBERHARD DA, FERRARA N: Complete inhibition of rhabdomyosarcoma xenograft growth and neovascularization requires blockade of both tumor and host vascular endothelial growth factor. Cancer Res. (2000) 60:6253–6258.
  • BORGSTROM P, HILLAN KJ, SRIMARARAO P, FERRARA N: Complete inhibition of angiogenesis and growth of microtumors by anti-vascular endothelial growth factor neutralizing antibody: novel concepts of angiostatic therapy from intravital videomicroscopy. Cancer Res. (1996) 56:4032–4039.
  • YUAN F, CHEN Y, DELLIAN M et al: Time-dependent vascular regression and permeability changes in established human tumor xenografts induced by an anti-vascular endothelial growth factor/vascular permeability factor antibody. Proc. Natl. Acad. Si". USA (1996) 93:14765–14770.
  • MESIANO S, FERRARA N, JAFFE RB: Role of vascular endothelial growth factor in ovarian cancer. Inhibition of Ascites formation by immunoneutralization. Am. J. Pathol (1998) 153:1249–1256.
  • MELNYK 0, ZIMMERMAN M, KIM KJ, SHUMAN M: Neutralizing anti-vascular endothelial growth factor antibody inhibits further growth of established prostate cancer and metastases in a pre-clinical model. Urol. (1999) 161:960–963.
  • BORGSTROM P, GOLD EP, HILLAN KJ, FERRARA N: Importance of VEGF for breast cancer angiogenesis in vivo implications from intravital microscopy of combination treatments with an anti-VEGF neutralizing monoclonal antibody and doxorubicin. Anticancer Res. (1999) 19:4203–4214.
  • LEE CG, HEIJN M, DI TOMASO E et al: Anti-vascular endothelial growth factor treatment augments tumor radiation response under normoxic or hypoxic conditions. Cancer Res. (2000) 60:5565–5570.
  • BENJAMIN LE, GOLIJANIN D, ITIN A, PODE D, KESHET E: Selective ablation of immature blood vessels in established human tumors follows vascular endothelial growth factor withdrawal. I Clin. Invest. (1999) 103:159–165.
  • •An elegant demonstration that VEGF is a survival factor for immature blood vessels.
  • GORSKI DH, BECKETT MA, JASKOWIAK NT et al.: Blockade of the vascular endothelial growth factor stress response increases the antitumor effects of ionizing radiation. Cancer Res. (1999) 59:3374–3378.
  • RYAN AM, BATES-EPPLER D, HAGLER KE et al.: Preclinical safety evaluation of rhuMAbVEGF an antiangiogenic humanized monoclonal antibody. Toxicol Pathol (1999) 27:78–86.
  • 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.
  • •Phase I tolerability data for antiVEGF therapy with no Grade II - IV adverse events but some tumour-related bleeding.
  • MARGOLIN K, GORDON MS, HOLMGREN E et al.: Phase lb 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 (2001) 19:851–856.
  • SLEDGE G, MILLER K, NOVOTNY W et al.: A Phase II trial of single-agent RhumAb VEGF (recombinant humanized monoclonal antibody to vascular endothelial cell growth factor) in patients with relapsed metastatic breast cancer. Proc. Am. Soc. Clin. Oncol(2000) 19:5C.
  • LANGMUIR VK, COBLEIGH MA, HERBST RS et al.: Successful long-term therapy with bevacizumab (Avastin) in solid tumors. Proc. Am. Soc. Clin. Oncol (2002) 21 (Abstract 32).
  • YANG JC, HAWORTH L, STEINBERG SM et al.: 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).
  • 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) 20:2247.
  • JOHNSON DH, DEVORE R, KABBINA VAR F et al.: Carboplatin (C) + paclitaxel (T) + RhuMAb-VEGF (AVF) may prolong survival in advanced non-squamous lung cancer. Proc. Am. Soc. Clin. Oncol (2001) 20:1256.
  • ASANO M, YUKITA A, SUZUKI H: Wide spectrum of antitumor activity of a neutralizing monoclonal antibody to human vascular endothelial growth factor. fpn..1. Cancer Res. (1999) 90:93–100.
  • JAYSON GC, MULATERO C, RANSON M et al.: Anti-VEGF antibody HuMV833:an EORTC biological treatment development group Phase I toxicity, pharmacokinetic and pharmacodynamic study. Proc. Am. Soc. Clin. Oncol. (2001) 20:14.
  • ZHU Z, LU D, KOTANIDES H et al.: Inhibition of vascular endothelial growth factor induced mitogenesis of human endothelial cells by a chimeric anti-kinase insert domain-containing receptor antibody. Cancer Lett. (1999) 136:203–213.
  • LU D, KUSSIE P, PYTOWSKI B et al.: Identification of the residues in the extracellular region of KDR important for interaction with vascular endothelial growth factor and neutralizing anti-KDR antibodies. J. Biol. Chem. (2000) 275:14321–14330.
  • PREWETT M, HUBER J, LI Y et al: Antivascular endothelial growth factor receptor (fetal liver kinase 1) monoclonal antibody inhibits tumor angiogenesis and growth of several mouse and human tumors. Cancer Res. (1999) 59:5209–5218.
  • KLEMENT G, BARUCHEL S, RAK J et al.: Continuous low-dose therapy with vinblastine and VEGF receptor-2 antibody induces sustained tumor regression without overt toxicity. Clin. Invest. (2000) 105:R15–R24.
  • •Compelling evidence of sustained tumour regression by combining chronic low dose chemotherapy with antiVEGFR-2 antibody treatment.
  • KOZIN SV, BOUCHER Y, HICKLIN DJ, BOHLEN P, JAIN RK, SUIT HD: Vascular endothelial growth factor receptor-2-blocking antibody potentiates radiation-induced long-term control of human tumor xenografts. Cancer Res. (2001) 61:39–44.
  • RUBENSTEIN JL, KIM J, OZAWA T et al.: Anti-VEGF antibody treatment of glioblastoma prolongs survival but results in increased vascular cooption. Neoplasia (2000) 4:306–314.
  • •Study showing vessel co-option as a resistance mechanism to antiangiogenic therapy.
  • KUNKEL P, ULBRICHT U, BOHLEN P et al.: Inhibition of glioblastoma angiogenesis and growth in vivo by systemic treatment with a monoclonal antibody against vascular endothelial growth factor receptor-2. Cancer Res. (2001) 61:6624–6628.
  • KADAMBI A, CARREIRA CM, YUN CO et al.: Vascular endothelial growth factor (VEGF)-C differentially affects tumor vascular function and leukocyte recruitment: role of VEGF-receptor 2 and host VEGF-A. Cancer Res. (2001) 61:2404–2408.
  • ••
  • MILLAUER B, SHAWVER LK, PLATE KH, RISAU W, ULLRICH A: Glioblastoma growth inhibited in vivo by a dominant-negative Flk-1 mutant. Nature (1994) 367:576–579.
  • PARRY TJ, CUSHMAN C, GALLEGOS AM et al.: Bioactivity of anti-angiogenic ribozymes targeting Fit-1 and KDR mRNA. Nucleic Acids Res. (1999) 27:2569–2577.
  • PAVCO PA, BOUHANA KS, GALLEGOS AM et al.: Antitumor and antimetastatic activity of ribozymes targeting the messenger RNA of vascular endothelial growth factor receptors. Clin. Cancer Res. (2000) 6:2094–2103.
  • SANDBERG JA, BOUHANA KS, GALLEGOS AM et al.: Pharmacokinetics of an antiangiogenic ribozyme (ANGIOZYME) in the mouse. Antisense Nucleic Acid Drug Dev. (1999) 9:271–277.
  • SANDBERG JA, SPROUL CD, BLANCHARD KS et al.: Acute toxicology and pharmacokinetic assessment of a ribozyme (ANGIOZYME) targeting vascular endothelial growth factor receptor mRNA in the cynomolgus monkey. Antisense Nucleic Add Drug Dev. (2000) 10:153–162.
  • SANDBERG JA, PARKER VP, BLANCHARD KS et al.: Pharmacokinetics and tolerability of an antiangiogenic ribozyme (ANGIOZYME) in healthy volunteers. Clin. Pharmacol (2000) 40:1462–1469.
  • VVENG DE, USMAN N: Angiozyme: a novel angiogenesis inhibitor. Can: Oricol Rep. (2000) 3:141–146.
  • VVENG DE, VVEISS P, KELLACKEY C et al.: Angiozyme pharmacokinetic and safety results: a Phase i/ii study in patients with refractory solid tumors. Proc. Am. Soc. Clin. Omni (2001):393 (Abstract).
  • HORNIG C, BARLEON B, AHMAD S et al.: Release and complex formation of soluble VEGFR-1 from endothelial cells and biological fluids. Lab. Invest. (2000) 80(4):443–454.
  • BELGORE FM, BLANN AD, LIP GY: Measurement of free and complexed soluble vascular endothelial growth factor receptor, Flt-1, in fluid samples: development and application of two new immunoassays. Clin. Sci. (2001) 100(5):567–575.
  • SHIBUYA M: Structure and dual function of vascular endothelial growth factor receptor-1 (Flt-1). Int. Biochem. Cell Biol. (2001) 33(4):409–420.
  • GERBER HP, VU TH, RYAN AM et al: VEGF couples hypertrophic cartilage remodeling, ossification and angiogenesis during endochondral bone formation. Nat. Med. (1999) 5:623–628.
  • FERRARA N, CHEN H, DAVIS-SMYTH T et al.: Vascular endothelial growth factor is essential for corpus luteum angiogenesis. Nat. Med. (1998) 4(3):336–340.
  • LIN P, SANKAR S, SHAN S et al.: Inhibition of tumor growth by targeting tumor endothelium using a soluble vascular endothelial growth factor receptor. Cell Growth Differ. (1998) 9(1):49–58.
  • KUO CJ, FARNEBO F, YU EY et al: Comparative evaluation of the antitumor activity of antiangiogenic proteins delivered by gene transfer. Proc. Natl. Acad. Sci.USA (2001) 98(8):4605–4610.
  • COLE PA, SONDHI D, KIM K: Chemical approaches to the study of protein tyrosine kinases and their implications for mechanism and inhibitor design. Pharmacol Ther. (1999) 82:219–229.
  • MENDEL DB, LAIRD AD, SMOLICH BD et al.: Development of SU5416, a selective small molecule inhibitor of VEGF receptor tyrosine kinase activity, as an anti-angiogenesis agent. Anti-Cancer Drug Design (2000) 15:29–41.
  • •In depth review on development of SU5416.
  • FABBRO F, MANLEY PW: 5U6668. Curc Opin. Investig. Drugs (2001) 2:1142–1148.
  • BUZZETTI F, BRASCA MG, CRUGNOLA A et al.: Cinnamamide analogs as inhibitors of protein tyrosine kinases. Farmaco (1993) 48:615–636.
  • •Discovery of 3-substituted indolin-2-ones as tyrosine kinase inhibitors.
  • SUN L, TRAN H, LIANG C et al: Identification of substituted 3-[(4,5,6,7-tetrahydro-1H-indo1-2-yOmethylene]-1,3-dihydroindol-2-ones as growth factor receptor inhibitors for VEGF-R2 (Flk-1/KDR), FGF-R1, and PDGF-R.13 tyrosine kinases. I Med. Chem. (2000) 43:2655–2663.
  • 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. Med. Chem. (1998) 41:2588–2603.
  • •Elaboration of indolin-2-ones as tyrosine kinase inhibitors.
  • 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.
  • ••Study of mechanism of kinase inhibitionand antiturnour effects of 5U6668 in mice.
  • KRYSTAL GW, HONSAWEK S, KIEWLICH D et al.: Indolinone tyrosine kinase inhibitors block Kit activation and growth of small-cell lung cancer cells. Cancer Res. (2001) 61:3660–3668.
  • MANLEY PW, FURET P: Prospects for anti-angiogenic therapies based upon VEGF inhibition. In: ACS Volume Anti-Cancer Agents: Frontiers in Cancer ChemotherapyI Ojima, G Vite, K Altmann (Eds) ACS Symposium Series 796, American Chemical Society, Washington DC (2001):282–298.
  • FONG TAT, 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 vascularisation and growth of multiple tumor types. Cancer Res. (1999) 59:99–106.
  • VAJKOCZY P, MENGER MD, VOLLMAR B et a/.: Inhibition of tumor growth, angiogenesis, and microcirculation by the novel Flk-1 inhibitor SU5416 as assessed by intravital multifluorescence videomicroscopy. Neoplasia (1999) 1:31–41.
  • VAJKOCZY P, MENGER MD, GOLDBRUNNER R et al.: Targeting angiogenesis inhibits tumor infiltration and expression of the proinvasive protein SPARC. bt.j Cancer (2000) 87:261–268.
  • SHAHEEN RM, DAVIS DW, LIU W et al.: Antiangiogenic therapy targeting the tyrosine kinase receptor for vascular endothelial growth factor receptor inhibits the growth of colon cancer liver metastasis and induced tumor and endothelial cell apoptosis. Cancer Res. (1999) 59:5412–5416.
  • ANGELOV L, SALHIA B, RONCARI L et al.: Inhibition of Angiogenesis by Blocking Activation of the Vascular Endothelial Growth Factor Receptor 2 Leads to Decreased Growth of Neurogenic Sarcomas. Cancer Res. (1999) 59:5536–5541.
  • KUENEN BC, ROSEN L, SMIT EF et al.: Dose-Finding and Pharmacokinetic Study of Cisplatin, Gemcitabine, and SU5416 in Patients with Solid Tumors. I Clin. Oncol (2002) 20:1657–1667.
  • •First clinical study showing potential toxicity of SU5416.
  • ANTONIAN L, ZHANG H, YANG C et al.: Biotransformation of the anti-angiogenic compound SU5416. Drug Metab. Dispos. (2000) 28:1505–1512.
  • ROSEN PJ, AMADO R, HECHT JR et al: A Phase I/II Study of 5U5416 in combination with 5-FU/leucovorin in patients with metastatic colorectal cancer. Proc. Am. Soc. Clin. Oncol (2001) 20:389 (Abstract).
  • SMOLICH BD, YUEN HA, WEST KA et al.: The antiangiogenic protein kinase inhibitors 5U5416 and 5U6668 inhibit the SCF receptor (c-kit) in a human myeloid leukemia cell line and in acute myeloid leukemia blasts. Blood (2001) 97:1413–1421.
  • MESTERS RM, PADRO T, BIEKER R et al.: Stable remission after administration of the receptor tyrosine kinase inhibitor 5U5416 in a patient with refractory acute myeloid leukemia. Blood (2001) 98:241–243.
  • HARRIS AL: Von Hippel-Lindau syndrome: target for anti-vascular endothelial growth factor (VEGF) receptor therapy. Oncologist (2000) 5:32–36.
  • ROSEN L, HANNAH A, ROSEN P et al: Phase I experience with oral 5U006668, a novel multiple receptor tyrosine kinase inhibitor in patients with advanced malignancies. I I th NCI-EORTC-AACR Symposium on New Drugs in Cancer Therapy Amsterdam, NL (2000):581 (Abstract).
  • ROSEN LS, ROSEN PJ, KABBINAVARF et al.: Phase I experience with 5U6668, a novel multiple receptor tyrosine kinase inhibitor in patients with advanced malignancies. Proc. Am. Soc. Clin. Oncol (2001) 20:383 (Abstract).
  • ABRAMS TJ, LEE LB, MURRAY LJ, MENDEL DB, CHERRINGTON JM: Inhibition of Kit-positive SCLC growth by SU11248, a novel tyrosine kinase inhibitor. 93rd Annual Meeting of the AACR Symposium on Molecular Targets and Cancer Therapeutics, San Francisco, CA,USA (2002):1669 (Abstract).
  • BOLD G, ALTMANN KH, FREI J et al: New anilinophthalazines as potent and orally well absorbed inhibitors of the VEGF receptor tyrosine kinases useful as antagonists of tumor-driven angiogenesis. Med. Chem. (2000) 43:2310–2323.
  • •Discovery of phthalazines as tyrosine kinase inhibitors.
  • 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.
  • 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.f Clin. Cancer Res. (2000) 6:957–965.
  • HESS C, VUONG V, HEGYL I et al: Effect of VEGF receptor inhibitor PTK787/ZK222548 combined with ionizing radiation on endothelial cells and tumour growth. Br. Cancer (2001) 85:2010–2016.
  • OZAKI H, SEO M, OZAKI K et al: Blockade of VEGF receptor signaling is sufficient to completely prevent retinal neovascularization. Am. Pathol (2000) 156:697–707.
  • KWAK N, OKAMOTO N, WOOD JM, CAMPOCHIARO PA: VEGF is major stimulator in model of choroidal neovascularization. Invest. Ophtharnol Vis. Sci. (2000) 41:3158–3164.
  • DREVS J, MROSS K, FUXIUS S et al: A Phase-1 dose-escalating and pharmacokinetic (PK) study of the VEGF-receptor-inhibitor PTK787/ZK222584 (PTK/ZK) in patients with liver metastasis of advanced cancer. Proc. Am. Soc. Gin. Oncol (2001) 20:398 (Abstract).
  • THOMAS A, MORGON B, DREVS J et al.: Pharmacodynamic results using dynamic contrast enhanced magnetic resonance imaging, of 2 Phase I studies of the VEGF inhibitor PTK787/ZK 222584 in Patients with Liver Metastases from Colorectal Cancer. Proc. Am. Soc. Clin. Oncol (2001) 20:279 (Abstract).
  • HENNEQUIN LF, STOKES ES, THOMAS AP et al.: 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. Med. Chem. (2002) 45:1300–1312.
  • HENNEQUIN LF, THOMAS AP, JOHNSTONE C et al.: Design and structure-activity relationship of a new class of potent VEGF receptor tyrosine kinase inhibitors. J. Med. Chem. (1999) 42:5369–5389.
  • •Discovery of quinazoline VEGFR kinase inhibitors.
  • 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.
  • WEDGE SR, OGILVIE DJ, DUKES M et al.: VEGF Receptor tyrosine kinase inhibitors as potential anti-tumour agents. Proc. Am. Assoc. Cancer Res. (2000) 41:3610 (Abstract).
  • WEDGE SR, KENDREW J, KLINOWSKA T et al.: The VEGF receptor tyrosine kinase inhibitor ZD6474 is efficacious in a spontaneously metastatic human tumor model. Proceedings of the 12th AACR-NCI-EORTC International Conference, Molecular Targets and Cancer Therapeutics, Discovery, Biology, and Clinical Applications. Gin. Cancer Res. (2001) 7(Suppl.):4 (Abstract).
  • WEDGE SR, CHECKLY D, DUKES M et al.: Dynamic Contrast-enhanced MRI Study of Human Tumor Xenografts Treated with the VEGF Signalling Inhibitor ZD6474. Proc. Am. Assoc. Cancer Res. (2001) 42:581 (Abstract).
  • WEDGE SR, OGILVIE DJ, DUKES M et al.: Pharmacological Efficacy of ZD6474, a VEGF Receptor Tyrosine Kinase Inhibitor, in Rat. Proc. Am. Assoc. Cancer Res. (2001) 42:3126 (Abstract).
  • 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. Proceedings of the 12th AACR-NCI-EORTC International Conference, Molecular Targets and Cancer Therapeutics, Discovery, Biology, and Clinical Applications. Gin. Cancer Res. (2001) 7(Suppl.):5 (Abstract).
  • HURWITZ HI, ECKHARDT SG, HOLDEN SN et al: Phase I Pharmacokinetic and Biological Study of the Angiogenesis Inhibitor, ZD6474, in Patients with Solid Tumors. Proc. Am. Soc. Oncol (2001) 20:396 (Abstract).
  • RUGGERI BA, 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) 43:5347 (Abstract).
  • ••
  • PILI R, ROBINSON C, MORRIS C, DIONNE CA, ISAACS JT, RUGGERI BA: CEP-5214, a novel orally active inhibitor of vascular endothelial growth factor (VEGF) receptor tyrosine kinase and prostate tumor growth in vivo. Proceedings of the 12th AACR-NCI-EORTC International Conference, Molecular Targets and Cancer Therapeutics, Discovery, Biology, and Clinical Applications. Chn. Cancer Res. (2001) 7(Suppl.):27 (Abstract).
  • JONES-BOLIN S, HUNTER K, ZHAO B, RUGGERI BA: 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) 43:2601.
  • KARP DD, TOLCHER A, HEALEY D et al.: Preliminary pharmacokinetic (PK) characteristics of an oral vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitor (TKI), CP-547,632 in patients (pts) with advanced solid tumors. Proc. Am. Assoc. Cancer Res. (2002) 43:2753 (Abstract).
  • BILODEAU MT, COLL KE, CUNNINGHAM AM et al.: Design and synthesis of 1,5-diarylbenzimidazoles as inhibitors of the VEGF-receptor KDR. Abstr. Pap. Am. Chem. Soc. (2001) 221:MEDI–147.
  • HELL-POURMOJIB M, HILBERG F, HECKEL A, VAN MEEL J: BIBF1000:A novel and potent VEGFR-2 inhibitor inhibits proliferation and induces apoptosis of endothelial cells in vitro. Proceedings of the 12th AACR-NCI-EORTC International Conference, Molecular Targets and Cancer Therapeutics, Discovery, Biology, and Clinical Applications. Gin. Cancer Res. (2001) 7(Suppl.):23 (Abstract).
  • YU JL, RAK JVV, COOMBER BL et al: Effect of p53 status on tumor response to anti-angiogenic therapy. Science (2002) 295:156–158Key paper demonstrating that tumourgrowth can become resistant to antiangiogenic therapy.

Websites

  • www.datastarweb.com SCRIP DAILY ONLINE: Pharmacia drops lead anti-angiogenesis product (13 Feb 2002) 2720:23.

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.