Cancer Research CR EMT and Cancer Progression and Treatment
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wedge, S. R.
Right arrow Articles by Hennequin, L. F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wedge, S. R.
Right arrow Articles by Hennequin, L. F.
[Cancer Research 62, 4645-4655, August 15, 2002]
© 2002 American Association for Cancer Research

Experimental Therapeutics

ZD6474 Inhibits Vascular Endothelial Growth Factor Signaling, Angiogenesis, and Tumor Growth following Oral Administration

Stephen R. Wedge1, Donald J. Ogilvie, Michael Dukes, Jane Kendrew, Rosemary Chester, Janet A. Jackson, Sarah J. Boffey, Paula J. Valentine, Jon O. Curwen, Helen L. Musgrove, George A. Graham, Gareth D. Hughes, Andrew P. Thomas, Elaine S. E. Stokes, Brenda Curry, Graham H. P. Richmond, Peter F. Wadsworth, Alison L. Bigley and Laurent F. Hennequin

Departments of Cancer and Infection Research [S. R. W., D. J. O., M. D., J. K., R. C., J. A. J., S. J. B., P. J. V., J. O. C., H. L. M., G. A. G., G. D. H., A. P. T., E. S. E. S., B. C.] and Safety Assessment [G. H. P. R., P. F. W., A. L. B.], AstraZeneca, Cheshire SK10 4TG, United Kingdom, and AstraZeneca Pharma, Centre de Recherches, 51689 Reims Cedex 2, France [L. F. H.]

ZD6474 [N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazolin-4-amine]is a potent, p.o. active, low molecular weight inhibitor of kinase insert domain-containing receptor [KDR/vascular endothelial growth factor receptor (VEGFR) 2] tyrosine kinase activity (IC50 = 40 nM). This compound has some additional activity versus the tyrosine kinase activity of fms-like tyrosine kinase 4 (VEGFR3;IC50 = 110 nM) and epidermal growth factor receptor (EGFR/HER1; IC50 = 500 nM) and yet demonstrates selectivity against a range of other tyrosine and serine-threonine kinases. The activity of ZD6474 versus KDR tyrosine kinase translates into potent inhibition of vascular endothelial growth factor-A (VEGF)-stimulated endothelial cell (human umbilical vein endothelial cell) proliferation in vitro (IC50 = 60 nM). Selective inhibition of VEGF signaling has been demonstrated in vivo in a growth factor-induced hypotension model in anesthetized rat: administration of ZD6474 (2.5 mg/kg, i.v.) reversed a hypotensive change induced by VEGF (by 63%) but did not significantly affect that induced by basic fibroblast growth factor. Once-daily oral administration of ZD6474 to growing rats for 14 days produced a dose-dependent increase in the femoro-tibial epiphyseal growth plate zone of hypertrophy, which is consistent with inhibition of VEGF signaling and angiogenesis in vivo. Administration of 50 mg/kg/day ZD6474 (once-daily, p.o.) to athymic mice with intradermally implanted A549 tumor cells also inhibited tumor-induced neovascularization significantly (63% inhibition after 5 days; P < 0.001). Oral administration of ZD6474 to athymic mice bearing established (0.15–0.47 cm3), histologically distinct (lung, prostate, breast, ovarian, colon, or vulval) human tumor xenografts or after implantation of aggressive syngeneic rodent tumors (lung, melanoma) in immunocompetent mice, produced a dose-dependent inhibition of tumor growth in all cases. Statistically significant antitumor activity was evident in each model with at least 25 mg/kg ZD6474 once daily (P < 0.05, one-tailed t test). Histological analysis of Calu-6 tumors treated with 50 mg/kg/day ZD6474 for 24 days showed a significant reduction (>70%) in CD31 (endothelial cell) staining in nonnecrotic regions. ZD6474 also restrained growth of much larger (0.9 cm3 volume) Calu-6 lung tumor xenografts and induced profound regression in established PC-3 prostate tumors of 1.4 cm3 volume. ZD6474 is currently in Phase I clinical development as a once-daily oral therapy in patients with advanced cancer.




This article has been cited by other articles:


Home page
 JCOHome page
S. A. Wells Jr, J. E. Gosnell, R. F. Gagel, J. Moley, D. Pfister, J. A. Sosa, M. Skinner, A. Krebs, J. Vasselli, and M. Schlumberger
Vandetanib for the Treatment of Patients With Locally Advanced or Metastatic Hereditary Medullary Thyroid Cancer
J. Clin. Oncol., February 10, 2010; 28(5): 767 - 772.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
I. K. Demedts, K. Y. Vermaelen, and J. P. van Meerbeeck
Treatment of extensive-stage small cell lung carcinoma: current status and future prospects
Eur. Respir. J., January 1, 2010; 35(1): 202 - 215.
[Abstract] [Full Text] [PDF]

Home page
 Anticancer ResHome page
M. MEDINGER, N. ESSER, U. ZIRRGIEBEL, A. RYAN, J. M. JURGENSMEIER, and J. DREVS
Antitumor and Antiangiogenic Activity of Cediranib in a Preclinical Model of Renal Cell Carcinoma
Anticancer Res, December 1, 2009; 29(12): 5065 - 5076.
[Abstract] [Full Text] [PDF]

Home page
 Anticancer ResHome page
G. MINNITI, R. MUNI, G. LANZETTA, P. MARCHETTI, and R. M. ENRICI
Chemotherapy for Glioblastoma: Current Treatment and Future Perspectives for Cytotoxic and Targeted Agents
Anticancer Res, December 1, 2009; 29(12): 5171 - 5184.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
S. A. Wells Jr. and M. Santoro
Targeting the RET Pathway in Thyroid Cancer
Clin. Cancer Res., December 1, 2009; 15(23): 7119 - 7123.
[Abstract] [Full Text] [PDF]

Home page
 The OncologistHome page
M. Ray, R. Salgia, and E. E. Vokes
The Role of EGFR Inhibition in the Treatment of Non-Small Cell Lung Cancer
Oncologist, November 1, 2009; 14(11): 1116 - 1130.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
E. P. Jane, D. R. Premkumar, S. O. Addo-Yobo, and I. F. Pollack
Abrogation of Mitogen-Activated Protein Kinase and Akt Signaling by Vandetanib Synergistically Potentiates Histone Deacetylase Inhibitor-Induced Apoptosis in Human Glioma Cells
J. Pharmacol. Exp. Ther., October 1, 2009; 331(1): 327 - 337.
[Abstract] [Full Text] [PDF]

Home page
 Endocr Relat CancerHome page
N. Normanno, A. Morabito, A. De Luca, M. C. Piccirillo, M. Gallo, M. R Maiello, and F. Perrone
Target-based therapies in breast cancer: current status and future perspectives
Endocr. Relat. Cancer, September 1, 2009; 16(3): 675 - 702.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
M. P. Morelli, A. M. Brown, T. M. Pitts, J. J. Tentler, F. Ciardiello, A. Ryan, J. M. Jurgensmeier, and S. G. Eckhardt
Targeting vascular endothelial growth factor receptor-1 and -3 with cediranib (AZD2171): effects on migration and invasion of gastrointestinal cancer cell lines
Mol. Cancer Ther., September 1, 2009; 8(9): 2546 - 2558.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
L. Horn and A. Sandler
Epidermal Growth Factor Receptor Inhibitors and Antiangiogenic Agents for the Treatment of Non-Small Cell Lung Cancer
Clin. Cancer Res., August 15, 2009; 15(16): 5040 - 5048.
[Abstract] [Full Text] [PDF]

Home page
 Anticancer ResHome page
D. W. SIEMANN, C. M. NORRIS, A. RYAN, and W. SHI
Impact of Tumor Cell VEGF Expression on the In Vivo Efficacy of Vandetanib (ZACTIMATM; ZD6474)
Anticancer Res, June 1, 2009; 29(6): 1987 - 1992.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
R. B. Natale, D. Bodkin, R. Govindan, B. G. Sleckman, N. A. Rizvi, A. Capo, P. Germonpre, W. E.E. Eberhardt, P. K. Stockman, S. J. Kennedy, et al.
Vandetanib Versus Gefitinib in Patients With Advanced Non-Small-Cell Lung Cancer: Results From a Two-Part, Double-Blind, Randomized Phase II Study
J. Clin. Oncol., May 20, 2009; 27(15): 2523 - 2529.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
G. N. Naumov, M. B. Nilsson, T. Cascone, A. Briggs, O. Straume, L. A. Akslen, E. Lifshits, L. A. Byers, L. Xu, H.-k. Wu, et al.
Combined Vascular Endothelial Growth Factor Receptor and Epidermal Growth Factor Receptor (EGFR) Blockade Inhibits Tumor Growth in Xenograft Models of EGFR Inhibitor Resistance
Clin. Cancer Res., May 15, 2009; 15(10): 3484 - 3494.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
S. I. Sherman
Advances in Chemotherapy of Differentiated Epithelial and Medullary Thyroid Cancers
J. Clin. Endocrinol. Metab., May 1, 2009; 94(5): 1493 - 1499.
[Abstract] [Full Text] [PDF]

Home page
 Proc Am Thorac SocHome page
L. Horn and A. B. Sandler
Angiogenesis in the Treatment of Non-Small Cell Lung Cancer
Proceedings of the ATS, April 15, 2009; 6(2): 206 - 217.
[Abstract] [Full Text] [PDF]

Home page
 The OncologistHome page
A. Morabito, M. C. Piccirillo, F. Falasconi, G. De Feo, A. Del Giudice, J. Bryce, M. Di Maio, E. De Maio, N. Normanno, and F. Perrone
Vandetanib (ZD6474), a Dual Inhibitor of Vascular Endothelial Growth Factor Receptor (VEGFR) and Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinases: Current Status and Future Directions
Oncologist, April 1, 2009; 14(4): 378 - 390.
[Abstract] [Full Text] [PDF]

Home page
 The OncologistHome page
N. A. Pennell and T. J. Lynch Jr.
Combined Inhibition of the VEGFR and EGFR Signaling Pathways in the Treatment of NSCLC
Oncologist, April 1, 2009; 14(4): 399 - 411.
[Abstract] [Full Text] [PDF]

Home page
 Ann OncolHome page
R. de Boer, Y. Humblet, J. Wolf, L. Nogova, K. Ruffert, T. Milenkova, R. Smith, A. Godwood, and J. Vansteenkiste
An open-label study of vandetanib with pemetrexed in patients with previously treated non-small-cell lung cancer
Ann. Onc., March 1, 2009; 20(3): 486 - 491.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
J. V. Heymach, L. Paz-Ares, F. De Braud, M. Sebastian, D. J. Stewart, W. E.E. Eberhardt, A. A. Ranade, G. Cohen, J. M. Trigo, A. B. Sandler, et al.
Randomized Phase II Study of Vandetanib Alone or With Paclitaxel and Carboplatin as First-Line Treatment for Advanced Non-Small-Cell Lung Cancer
J. Clin. Oncol., November 20, 2008; 26(33): 5407 - 5415.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
W. Ren, B. Korchin, G. Lahat, C. Wei, S. Bolshakov, T. Nguyen, W. Merritt, A. Dicker, A. Lazar, A. Sood, et al.
Combined Vascular Endothelial Growth Factor Receptor/Epidermal Growth Factor Receptor Blockade with Chemotherapy for Treatment of Local, Uterine, and Metastatic Soft Tissue Sarcoma
Clin. Cancer Res., September 1, 2008; 14(17): 5466 - 5475.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
S. Choi, D. Sano, M. Cheung, M. Zhao, S. A. Jasser, A. J. Ryan, L. Mao, W.-T. Chen, A. K. El-Naggar, and J. N. Myers
Vandetanib Inhibits Growth of Adenoid Cystic Carcinoma in an Orthotopic Nude Mouse Model
Clin. Cancer Res., August 15, 2008; 14(16): 5081 - 5089.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
R. Bianco, R. Rosa, V. Damiano, G. Daniele, T. Gelardi, S. Garofalo, V. Tarallo, S. De Falco, D. Melisi, R. Benelli, et al.
Vascular Endothelial Growth Factor Receptor-1 Contributes to Resistance to Anti-Epidermal Growth Factor Receptor Drugs in Human Cancer Cells
Clin. Cancer Res., August 15, 2008; 14(16): 5069 - 5080.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
T. P. Padera, A. H. Kuo, T. Hoshida, S. Liao, J. Lobo, K. R. Kozak, D. Fukumura, and R. K. Jain
Differential response of primary tumor versus lymphatic metastasis to VEGFR-2 and VEGFR-3 kinase inhibitors cediranib and vandetanib
Mol. Cancer Ther., August 1, 2008; 7(8): 2272 - 2279.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
D. Alferez, R. W. Wilkinson, J. Watkins, R. Poulsom, N. Mandir, S. R. Wedge, I. T. Pyrah, N. R. Smith, L. Jackson, A. J. Ryan, et al.
Dual inhibition of VEGFR and EGFR signaling reduces the incidence and size of intestinal adenomas in ApcMin/+ mice
Mol. Cancer Ther., March 1, 2008; 7(3): 590 - 598.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
A. Claes, P. Wesseling, J. Jeuken, C. Maass, A. Heerschap, and W. P.J. Leenders
Antiangiogenic compounds interfere with chemotherapy of brain tumors due to vessel normalization
Mol. Cancer Ther., January 1, 2008; 7(1): 71 - 78.
[Abstract] [Full Text] [PDF]

Home page
 Endocr Relat CancerHome page
G. Riesco-Eizaguirre and P. Santisteban
New insights in thyroid follicular cell biology and its impact in thyroid cancer therapy
Endocr. Relat. Cancer, December 1, 2007; 14(4): 957 - 977.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
T. Troiani, N. J. Serkova, D. L. Gustafson, T. K. Henthorn, O. Lockerbie, A. Merz, M. Long, M. Morrow, F. Ciardiello, and S. G. Eckhardt
Investigation of Two Dosing Schedules of Vandetanib (ZD6474), an Inhibitor of Vascular Endothelial Growth Factor Receptor and Epidermal Growth Factor Receptor Signaling, in Combination with Irinotecan in a Human Colon Cancer Xenograft Model
Clin. Cancer Res., November 1, 2007; 13(21): 6450 - 6458.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
M. Llamazares, A. J. Obaya, A. Moncada-Pazos, R. Heljasvaara, J. Espada, C. Lopez-Otin, and S. Cal
The ADAMTS12 metalloproteinase exhibits anti-tumorigenic properties through modulation of the Ras-dependent ERK signalling pathway
J. Cell Sci., October 15, 2007; 120(20): 3544 - 3552.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
J. V. Heymach, B. E. Johnson, D. Prager, E. Csada, J. Roubec, M. Pesek, I. Spasova, C. P. Belani, I. Bodrogi, S. Gadgeel, et al.
Randomized, Placebo-Controlled Phase II Study of Vandetanib Plus Docetaxel in Previously Treated Non Small-Cell Lung Cancer
J. Clin. Oncol., September 20, 2007; 25(27): 4270 - 4277.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
N. R. Smith, N. H. James, I. Oakley, A. Wainwright, C. Copley, J. Kendrew, L. M. Womersley, J. M. Jurgensmeier, S. R. Wedge, and S. T. Barry
Acute pharmacodynamic and antivascular effects of the vascular endothelial growth factor signaling inhibitor AZD2171 in Calu-6 human lung tumor xenografts
Mol. Cancer Ther., August 1, 2007; 6(8): 2198 - 2208.
[Abstract] [Full Text] [PDF]

Home page
 Endocr Relat CancerHome page
V. Johanson, H. Ahlman, P. Bernhardt, S. Jansson, L. Kolby, F. Persson, G. Stenman, C. Sward, B. Wangberg, M. Stridsberg, et al.
A transplantable human medullary thyroid carcinoma as a model for RET tyrosine kinase-driven tumorigenesis
Endocr. Relat. Cancer, June 1, 2007; 14(2): 433 - 444.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
G. Giaccone
The Potential of Antiangiogenic Therapy in Non-Small Cell Lung Cancer
Clin. Cancer Res., April 1, 2007; 13(7): 1961 - 1970.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
L. Q.M. Chow and S. G. Eckhardt
Sunitinib: From Rational Design to Clinical Efficacy
J. Clin. Oncol., March 1, 2007; 25(7): 884 - 896.
[Abstract] [Full Text] [PDF]

Home page
 Mol Cancer ResHome page
J. Tabernero
The Role of VEGF and EGFR Inhibition: Implications for Combining Anti-VEGF and Anti-EGFR Agents
Mol. Cancer Res., March 1, 2007; 5(3): 203 - 220.
[Abstract] [Full Text] [PDF]

Home page
 The OncologistHome page
L. V. Sequist
Second-Generation Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Non-Small Cell Lung Cancer
Oncologist, March 1, 2007; 12(3): 325 - 330.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
W. Wu, A. Onn, T. Isobe, S. Itasaka, R. R. Langley, T. Shitani, K. Shibuya, R. Komaki, A. J. Ryan, I. J. Fidler, et al.
Targeted therapy of orthotopic human lung cancer by combined vascular endothelial growth factor and epidermal growth factor receptor signaling blockade
Mol. Cancer Ther., February 1, 2007; 6(2): 471 - 483.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
M. R. Horsman and D. W. Siemann
Pathophysiologic Effects of Vascular-Targeting Agents and the Implications for Combination with Conventional Therapies
Cancer Res., December 15, 2006; 66(24): 11520 - 11539.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
P. Hammarsten, S. Halin, P. Wikstom, R. Henriksson, S. H. Rudolfsson, and A. Bergh
Inhibitory Effects of Castration in an Orthotopic Model of Androgen-Independent Prostate Cancer Can Be Mimicked and Enhanced by Angiogenesis Inhibition
Clin. Cancer Res., December 15, 2006; 12(24): 7431 - 7436.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
C. Cao, J. M. Albert, L. Geng, P. S. Ivy, A. Sandler, D. H. Johnson, and B. Lu
Vascular Endothelial Growth Factor Tyrosine Kinase Inhibitor AZD2171 and Fractionated Radiotherapy in Mouse Models of Lung Cancer
Cancer Res., December 1, 2006; 66(23): 11409 - 11415.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
C. Bianco, E. Giovannetti, F. Ciardiello, V. Mey, S. Nannizzi, G. Tortora, T. Troiani, F. Pasqualetti, G. Eckhardt, M. de Liguoro, et al.
Synergistic Antitumor Activity of ZD6474, An Inhibitor of Vascular Endothelial Growth Factor Receptor and Epidermal Growth Factor Receptor Signaling, with Gemcitabine and Ionizing Radiation against Pancreatic Cancer
Clin. Cancer Res., December 1, 2006; 12(23): 7099 - 7107.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
E. Kamoshita, Y. Ikeda, M. Fujita, H. Amano, A. Oikawa, T. Suzuki, Y. Ogawa, S. Yamashina, S. Azuma, S. Narumiya, et al.
Recruitment of a Prostaglandin E Receptor Subtype, EP3-Expressing Bone Marrow Cells Is Crucial in Wound-Induced Angiogenesis
Am. J. Pathol., October 1, 2006; 169(4): 1458 - 1472.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
D. L. Gustafson, E. L. Bradshaw-Pierce, A. L. Merz, and J. A. Zirrolli
Tissue Distribution and Metabolism of the Tyrosine Kinase Inhibitor ZD6474 (Zactima) in Tumor-Bearing Nude Mice following Oral Dosing
J. Pharmacol. Exp. Ther., August 1, 2006; 318(2): 872 - 880.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
T. Troiani, O. Lockerbie, M. Morrow, F. Ciardiello, and S. G. Eckhardt
Sequence-dependent inhibition of human colon cancer cell growth and of prosurvival pathways by oxaliplatin in combination with ZD6474 (Zactima), an inhibitor of VEGFR and EGFR tyrosine kinases.
Mol. Cancer Ther., July 1, 2006; 5(7): 1883 - 1894.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
O. Potapova, A. D. Laird, M. A. Nannini, A. Barone, G. Li, K. G. Moss, J. M. Cherrington, and D. B. Mendel
Contribution of individual targets to the antitumor efficacy of the multitargeted receptor tyrosine kinase inhibitor SU11248
Mol. Cancer Ther., May 1, 2006; 5(5): 1280 - 1289.
[Abstract] [Full Text] [PDF]

Home page
 JNCI J Natl Cancer InstHome page
F. Carlomagno, S. Anaganti, T. Guida, G. Salvatore, G. Troncone, S. M. Wilhelm, and M. Santoro
BAY 43-9006 inhibition of oncogenic RET mutants.
J Natl Cancer Inst, March 1, 2006; 98(5): 326 - 334.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
N. Amino, Y. Ideyama, M. Yamano, S. Kuromitsu, K. Tajinda, K. Samizu, H. Hisamichi, A. Matsuhisa, K. Shirasuna, M. Kudoh, et al.
YM-359445, an Orally Bioavailable Vascular Endothelial Growth Factor Receptor-2 Tyrosine Kinase Inhibitor, Has Highly Potent Antitumor Activity against Established Tumors
Clin. Cancer Res., March 1, 2006; 12(5): 1630 - 1638.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
S. S. Singhal, Y. C. Awasthi, and S. Awasthi
Regression of Melanoma in a Murine Model by RLIP76 Depletion
Cancer Res., February 15, 2006; 66(4): 2354 - 2360.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
A. J. Garton, A. P.A. Crew, M. Franklin, A. R. Cooke, G. M. Wynne, L. Castaldo, J. Kahler, S. L. Winski, A. Franks, E. N. Brown, et al.
OSI-930: A Novel Selective Inhibitor of Kit and Kinase Insert Domain Receptor Tyrosine Kinases with Antitumor Activity in Mouse Xenograft Models
Cancer Res., January 15, 2006; 66(2): 1015 - 1024.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
K. D. Miller, M. Miller, S. Mehrotra, B. Agarwal, B. H. Mock, Q.-H. Zheng, S. Badve, G. D. Hutchins, and G. W. Sledge Jr.
A Physiologic Imaging Pilot Study of Breast Cancer Treated with AZD2171
Clin. Cancer Res., January 1, 2006; 12(1): 281 - 288.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
S. Yano, H. Muguruma, Y. Matsumori, H. Goto, E. Nakataki, N. Edakuni, H. Tomimoto, S. Kakiuchi, A. Yamamoto, H. Uehara, et al.
Antitumor Vascular Strategy for Controlling Experimental Metastatic Spread of Human Small-Cell Lung Cancer Cells with ZD6474 in Natural Killer Cell-Depleted Severe Combined Immunodeficient Mice
Clin. Cancer Res., December 15, 2005; 11(24): 8789 - 8798.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
Y. Kitagawa, J. Dai, J. Zhang, J. M. Keller, J. Nor, Z. Yao, and E. T. Keller
Vascular Endothelial Growth Factor Contributes to Prostate Cancer-Mediated Osteoblastic Activity
Cancer Res., December 1, 2005; 65(23): 10921 - 10929.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
J. N. Rich, S. Sathornsumetee, S. T. Keir, M. W. Kieran, A. Laforme, A. Kaipainen, R. E. McLendon, M. W. Graner, B.K. A. Rasheed, L. Wang, et al.
ZD6474, a Novel Tyrosine Kinase Inhibitor of Vascular Endothelial Growth Factor Receptor and Epidermal Growth Factor Receptor, Inhibits Tumor Growth of Multiple Nervous System Tumors
Clin. Cancer Res., November 15, 2005; 11(22): 8145 - 8157.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
I. Roodink, J. Raats, B. van der Zwaag, K. Verrijp, B. Kusters, H. van Bokhoven, M. Linkels, R. M.W. de Waal, and W. P.J. Leenders
Plexin D1 Expression Is Induced on Tumor Vasculature and Tumor Cells: A Novel Target for Diagnosis and Therapy?
Cancer Res., September 15, 2005; 65(18): 8317 - 8323.
[Abstract] [Full Text] [PDF]

Home page
 Ann OncolHome page
S. N. Holden, S. G. Eckhardt, R. Basser, R. de Boer, D. Rischin, M. Green, M. A. Rosenthal, C. Wheeler, A. Barge, and H. I. Hurwitz
Clinical evaluation of ZD6474, an orally active inhibitor of VEGF and EGF receptor signaling, in patients with solid, malignant tumors
Ann. Onc., August 1, 2005; 16(8): 1391 - 1397.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
L. Ma, G. Francia, A. Viloria-Petit, D. J. Hicklin, J. du Manoir, J. Rak, and R. S. Kerbel
In vitro Procoagulant Activity Induced in Endothelial Cells by Chemotherapy and Antiangiogenic Drug Combinations: Modulation by Lower-Dose Chemotherapy
Cancer Res., June 15, 2005; 65(12): 5365 - 5373.
[Abstract] [Full Text] [PDF]

Home page
 The OncologistHome page
L. S. Rosen
VEGF-Targeted Therapy: Therapeutic Potential and Recent Advances
Oncologist, June 1, 2005; 10(6): 382 - 391.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
S. R. Wedge, J. Kendrew, L. F. Hennequin, P. J. Valentine, S. T. Barry, S. R. Brave, N. R. Smith, N. H. James, M. Dukes, J. O. Curwen, et al.
AZD2171: A Highly Potent, Orally Bioavailable, Vascular Endothelial Growth Factor Receptor-2 Tyrosine Kinase Inhibitor for the Treatment of Cancer
Cancer Res., May 15, 2005; 65(10): 4389 - 4400.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
R. S. Herbst, A. Onn, and A. Sandler
Angiogenesis and Lung Cancer: Prognostic and Therapeutic Implications
J. Clin. Oncol., May 10, 2005; 23(14): 3243 - 3256.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
M. Vidal, S. Wells, A. Ryan, and R. Cagan
ZD6474 Suppresses Oncogenic RET Isoforms in a Drosophila Model for Type 2 Multiple Endocrine Neoplasia Syndromes and Papillary Thyroid Carcinoma
Cancer Res., May 1, 2005; 65(9): 3538 - 3541.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
K. D. Miller, J. M. Trigo, C. Wheeler, A. Barge, J. Rowbottom, G. Sledge, and J. Baselga
A Multicenter Phase II Trial of ZD6474, a Vascular Endothelial Growth Factor Receptor-2 and Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor, in Patients with Previously Treated Metastatic Breast Cancer
Clin. Cancer Res., May 1, 2005; 11(9): 3369 - 3376.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
P. Beaudry, J. Force, G. N. Naumov, A. Wang, C. H. Baker, A. Ryan, S. Soker, B. E. Johnson, J. Folkman, and J. V. Heymach
Differential Effects of Vascular Endothelial Growth Factor Receptor-2 Inhibitor ZD6474 on Circulating Endothelial Progenitors and Mature Circulating Endothelial Cells: Implications for Use as a Surrogate Marker of Antiangiogenic Activity
Clin. Cancer Res., May 1, 2005; 11(9): 3514 - 3522.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
X.-F. Zhu, B.-F. Xie, J.-M. Zhou, G.-K. Feng, Z.-C. Liu, X.-Y. Wei, F.-X. Zhang, M.-F. Liu, and Y.-X. Zeng
Blockade of Vascular Endothelial Growth Factor Receptor Signal Pathway and Antitumor Activity of ON-III (2',4'-Dihydroxy-6'-methoxy-3',5'-dimethylchalcone), a Component from Chinese Herbal Medicine
Mol. Pharmacol., May 1, 2005; 67(5): 1444 - 1450.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
J. Baselga and C. L. Arteaga
Critical Update and Emerging Trends in Epidermal Growth Factor Receptor Targeting in Cancer
J. Clin. Oncol., April 10, 2005; 23(11): 2445 - 2459.
[Abstract] [Full Text] [PDF]

Home page
 Postgrad. Med. J.Home page
K Gupta and J Zhang
Angiogenesis: a curse or cure?
Postgrad. Med. J., April 1, 2005; 81(954): 236 - 242.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
M. Fujita, I. Hayashi, S. Yamashina, A. Fukamizu, M. Itoman, and M. Majima
Angiotensin type 1a receptor signaling-dependent induction of vascular endothelial growth factor in stroma is relevant to tumor-associated angiogenesis and tumor growth
Carcinogenesis, February 1, 2005; 26(2): 271 - 279.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
D. W. Siemann, M. C. Bibby, G. G. Dark, A. P. Dicker, F. A.L.M. Eskens, M. R. Horsman, D. Marme, and P. M. LoRusso
Differentiation and Definition of Vascular-Targeted Therapies
Clin. Cancer Res., January 15, 2005; 11(2): 416 - 420.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
K. J. Williams, B. A. Telfer, S. Brave, J. Kendrew, L. Whittaker, I. J. Stratford, and S. R. Wedge
ZD6474, a Potent Inhibitor of Vascular Endothelial Growth Factor Signaling, Combined With Radiotherapy: Schedule-Dependent Enhancement of Antitumor Activity
Clin. Cancer Res., December 15, 2004; 10(24): 8587 - 8593.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
B. Nicholson, K. Gulding, M. Conaway, S. R. Wedge, and D. Theodorescu
Combination Antiangiogenic and Androgen Deprivation Therapy for Prostate Cancer: A Promising Therapeutic Approach
Clin. Cancer Res., December 15, 2004; 10(24): 8728 - 8734.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
K. Nakamura, A. Yamamoto, M. Kamishohara, K. Takahashi, E. Taguchi, T. Miura, K. Kubo, M. Shibuya, and T. Isoe
KRN633: A selective inhibitor of vascular endothelial growth factor receptor-2 tyrosine kinase that suppresses tumor angiogenesis and growth
Mol. Cancer Ther., December 1, 2004; 3(12): 1639 - 1649.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
S. M. Wilhelm, C. Carter, L. Tang, D. Wilkie, A. McNabola, H. Rong, C. Chen, X. Zhang, P. Vincent, M. McHugh, et al.
BAY 43-9006 Exhibits Broad Spectrum Oral Antitumor Activity and Targets the RAF/MEK/ERK Pathway and Receptor Tyrosine Kinases Involved in Tumor Progression and Angiogenesis
Cancer Res., October 1, 2004; 64(19): 7099 - 7109.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
W. P. J. Leenders, B. Kusters, K. Verrijp, C. Maass, P. Wesseling, A. Heerschap, D. Ruiter, A. Ryan, and R. de Waal
Antiangiogenic Therapy of Cerebral Melanoma Metastases Results in Sustained Tumor Progression via Vessel Co-Option
Clin. Cancer Res., September 15, 2004; 10(18): 6222 - 6230.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
M. F. McCarty, J. Wey, O. Stoeltzing, W. Liu, F. Fan, C. Bucana, P. F. Mansfield, A. J. Ryan, and L. M. Ellis
ZD6474, a vascular endothelial growth factor receptor tyrosine kinase inhibitor with additional activity against epidermal growth factor receptor tyrosine kinase, inhibits orthotopic growth and angiogenesis of gastric cancer
Mol. Cancer Ther., September 1, 2004; 3(9): 1041 - 1048.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
S. Emanuel, R. H. Gruninger, A. Fuentes-Pesquera, P. J. Connolly, J. A. Seamon, S. Hazel, R. Tominovich, B. Hollister, C. Napier, M. R. D'Andrea, et al.
A Vascular Endothelial Growth Factor Receptor-2 Kinase Inhibitor Potentiates the Activity of the Conventional Chemotherapeutic Agents Paclitaxel and Doxorubicin in Tumor Xenograft Models
Mol. Pharmacol., September 1, 2004; 66(3): 635 - 647.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
P. Traxler, P. R. Allegrini, R. Brandt, J. Brueggen, R. Cozens, D. Fabbro, K. Grosios, H. A. Lane, P. McSheehy, J. Mestan, et al.
AEE788: A Dual Family Epidermal Growth Factor Receptor/ErbB2 and Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitor with Antitumor and Antiangiogenic Activity
Cancer Res., July 15, 2004; 64(14): 4931 - 4941.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
D. W. Davis, K. Inoue, C. P. N. Dinney, D. J. Hicklin, J. L. Abbruzzese, and D. J. McConkey
Regional Effects of an Antivascular Endothelial Growth Factor Receptor Monoclonal Antibody on Receptor Phosphorylation and Apoptosis in Human 253J B-V Bladder Cancer Xenografts
Cancer Res., July 1, 2004; 64(13): 4601 - 4610.
[Abstract] [Full Text] [PDF]

Home page
 The OncologistHome page
R. S. Herbst and A. B. Sandler
Non-Small Cell Lung Cancer and Antiangiogenic Therapy: What Can Be Expected of Bevacizumab?
Oncologist, June 1, 2004; 9(suppl_1): 19 - 26.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
S. H. Rudolfsson, P. Wikstrom, A. Jonsson, O. Collin, and A. Bergh
Hormonal Regulation and Functional Role of Vascular Endothelial Growth Factor A in the Rat Testis
Biol Reprod, February 1, 2004; 70(2): 340 - 347.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
L. Sepp-Lorenzino, E. Rands, X. Mao, B. Connolly, J. Shipman, J. Antanavage, S. Hill, L. Davis, S. Beck, K. Rickert, et al.
A Novel Orally Bioavailable Inhibitor of Kinase Insert Domain-Containing Receptor Induces Antiangiogenic Effects and Prevents Tumor Growth in Vivo
Cancer Res., January 15, 2004; 64(2): 751 - 756.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
F. Ciardiello, R. Bianco, R. Caputo, R. Caputo, V. Damiano, T. Troiani, D. Melisi, F. De Vita, S. De Placido, A. R. Bianco, et al.
Antitumor Activity of ZD6474, a Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitor, in Human Cancer Cells with Acquired Resistance to Antiepidermal Growth Factor Receptor Therapy
Clin. Cancer Res., January 15, 2004; 10(2): 784 - 793.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
J. S. Beebe, J. P. Jani, E. Knauth, P. Goodwin, C. Higdon, A. M. Rossi, E. Emerson, M. Finkelstein, E. Floyd, S. Harriman, et al.
Pharmacological Characterization of CP-547,632, a Novel Vascular Endothelial Growth Factor Receptor-2 Tyrosine Kinase Inhibitor for Cancer Therapy
Cancer Res., November 1, 2003; 63(21): 7301 - 7309.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
L. M. Ellis
Antiangiogenic Therapy: More Promise and, Yet Again, More Questions
J. Clin. Oncol., November 1, 2003; 21(21): 3897 - 3899.
[Full Text] [PDF]

Home page
 Mol Cancer ResHome page
G. Petrangolini, G. Pratesi, M. De Cesare, R. Supino, C. Pisano, M. Marcellini, V. Giordano, D. Laccabue, C. Lanzi, and F. Zunino
Antiangiogenic Effects of the Novel Camptothecin ST1481 (Gimatecan) in Human Tumor Xenografts
Mol. Cancer Res., October 1, 2003; 1(12): 863 - 870.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
B. Ruggeri, J. Singh, D. Gingrich, T. Angeles, M. Albom, H. Chang, C. Robinson, K. Hunter, P. Dobrzanski, S. Jones-Bolin, et al.
CEP-7055: A Novel, Orally Active Pan Inhibitor of Vascular Endothelial Growth Factor Receptor Tyrosine Kinases with Potent Antiangiogenic Activity and Antitumor Efficacy in Preclinical Models
Cancer Res., September 15, 2003; 63(18): 5978 - 5991.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
L. Zilberberg, S. Shinkaruk, O. Lequin, B. Rousseau, M. Hagedorn, F. Costa, D. Caronzolo, M. Balke, X. Canron, O. Convert, et al.
Structure and Inhibitory Effects on Angiogenesis and Tumor Development of a New Vascular Endothelial Growth Inhibitor
J. Biol. Chem., September 12, 2003; 278(37): 35564 - 35573.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
S. Williams, C. Pettaway, R. Song, C. Papandreou, C. Logothetis, and D. J. McConkey
Differential effects of the proteasome inhibitor bortezomib on apoptosis and angiogenesis in human prostate tumor xenografts
Mol. Cancer Ther., September 1, 2003; 2(9): 835 - 843.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
M. Braga-Basaria and M. D. Ringel
Beyond Radioiodine: A Review of Potential New Therapeutic Approaches for Thyroid Cancer
J. Clin. Endocrinol. Metab., May 1, 2003; 88(5): 1947 - 1960.
[Abstract] [Full Text] [PDF]

Home page
 JEMHome page
H. Amano, I. Hayashi, H. Endo, H. Kitasato, S. Yamashina, T. Maruyama, M. Kobayashi, K. Satoh, M. Narita, Y. Sugimoto, et al.
Host Prostaglandin E2-EP3 Signaling Regulates Tumor-Associated Angiogenesis and Tumor Growth
J. Exp. Med., January 20, 2003; 197(2): 221 - 232.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
F. Carlomagno, D. Vitagliano, T. Guida, F. Ciardiello, G. Tortora, G. Vecchio, A. J. Ryan, G. Fontanini, A. Fusco, and M. Santoro
ZD6474, an Orally Available Inhibitor of KDR Tyrosine Kinase Activity, Efficiently Blocks Oncogenic RET Kinases
Cancer Res., December 15, 2002; 62(24): 7284 - 7290.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2002 by the American Association for Cancer Research.