472
Views
85
CrossRef citations to date
0
Altmetric
REVIEW

Alpha-v Integrins as Therapeutic Targets in Oncology

, , , , , , , , & show all
Pages 632-646 | Published online: 11 Jun 2009

REFERENCES

  • Mizejewski G. J. Role of integrins in cancer: survey of expression patterns. Proc Soc Exp Biol Med. 1999; 222: 124–138
  • van der Flier A., Sonnenberg A. Function and interactions of integrins. Cell Tissue Res. 2001; 305: 285–298
  • Stupack D. G., Cheresh D. A. Get a ligand, get a life: integrins, signaling and cell survival. J Cell Sci. 2002; 115: 3729–3738, (Pt 19)
  • Merviel P., Challier J. C., Carbillon L., Foidart J. M., Uzan S. The role of integrins in human embryo implantation. Fetal Diagn Ther. 2001; 16(6)364–371
  • Schuppan D., Ocker M. Integrin-mediated control of cell growth. Hepatology. 2003; 38(2)289–291
  • Curley G. P., Blum H., Humphries M. J. Integrin antagonists. Cell Mol. Life Sci. 1999; 56(5–6)427–441
  • Hood J. D., Cheresh D. A. Role of integrins in cell invasion and migration. Nat. Rev Cancer. 2002; 2(2)91–100
  • Plow E. F., Haas T. A., Zhang L., Loftus J., Smith J. W. Ligand binding to integrins. J Biol Chem 2000; 275(29)21785–21788
  • Kerr J. S., Slee A. M., Mousa S. A. The alpha v integrin antagonists as novel anticancer agents: an update. Expert Opin Investig. Drugs 2002; 11(12)1765–1774
  • Guo W., Giancotti F. G. Integrin signalling during tumour progression. Nat. Rev. Mol. Cell Biol. 2004; 5(10)816–826
  • Gutheil J. C., Campbell T. N., Pierce P. R., Watkins J. D., Huse W. D., Bodkin D. J., Cheresh D. A. Targeted antiangiogenic therapy for cancer using Vitaxin: a humanized monoclonal antibody to the integrin alphavbeta3. Clin Cancer Res. 2000; 6(8)3056–3061
  • Patel S. R., Jenkins J., Papadopolous N., Burgess M. A., Plager C., Gutterman J., Benjamin R. S. Pilot study of vitaxin–an angiogenesis inhibitor-in patients with advanced leiomyosarcomas. Cancer. 2001; 92(5)1347–1348
  • Posey J. A., Khazaeli M. B., DelGrosso A., Saleh M. N., Lin C. Y., Huse W., LoBuglio A. F. A pilot trial of Vitaxin, a humanized anti-vitronectin receptor (anti alpha v beta 3) antibody in patients with metastatic cancer. Cancer Biother Radiopharm. 2001; 16(2)125–132
  • Eskens F., Dumez H., Verweij J., Perschl A., Kovar A., Brindley C., Van Oosterom A. Phase I and pharmacologic study of EMD 121974, an 3 and 5 integrin inhibitor that perturbs tumor angiogenesis, in patients with solid tumors. Presented at: 2000 ASCO Annual Meeting, Abstract 801
  • Eskens F., Dumez H., Verweij J., et al. Cilengitide (EMD 121974) inhibits angiogenesis by blocking α vβ 3 and α vβ 5 integrins; mature results of a phase I and pharmacological study. Abstract 296. Clin Cancer Res. 2000; 6, (suppl)
  • Nabors L. B., Rosenfeld S. S., Mikkelson T., et al. A phase I trial of EMD 121974 for treatment of patients with recurrent malignant gliomas. Abstract 236. J Neuro-Oncol. 2002; 4(4)
  • Eskens F. A., Dumez H., Hoekstra R., Perschl A., Brindley C., Bottcher S., Wynendaele W., Drevs J., Verweij J., van Oosterom A. T. Phase I and pharmacokinetic study of continuous twice weekly intravenous administration of Cilengitide (EMD 121974), a novel inhibitor of the integrins alphavbeta3 and alphavbeta5 in patients with advanced solid tumours. Eur J Cancer. 2003; 39(7)917–926
  • Damiano J. S., Cress A. E., Hazlehurst L. A., Shtil A. A., Dalton W. S. Cell adhesion mediated drug resistance (CAM-DR): role of integrins and resistance to apoptosis in human myeloma cell lines. Blood. 1999; 93(5)1658–1667
  • Jensen G. S., Belch A. R., Mant M. J., Ruether B. A., Yacyshyn B. R., Pilarski L. M. Expression of multiple beta 1 integrins on circulating monoclonal B cells in patients with multiple myeloma. Am J Hematol 1993; 43(1)29–36
  • Uchiyama H., Barut B. A., Chauhan D., Cannistra S. A., Anderson K. C. Characterization of adhesion molecules on human myeloma cell lines. Blood 1992; 80(9)2306–2314
  • Uchiyama H., Barut B. A., Mohrbacher A. F., Chauhan D., Anderson K. C. Adhesion of human myeloma-derived cell lines to bone marrow stromal cells stimulates interleukin-6 secretion. Blood. 1993; 82(12)3712–3720
  • Gupta D., Treon S. P., Shima Y., Hideshima T., Podar K., Tai Y. T., Lin B., Lentzsch S., Davies F. E., Chauhan D., Schlossman R. L., Richardson P., Ralph P., Wu L., Payvandi F., Muller G., Stirling D. I., Anderson K. C. Adherence of multiple myeloma cells to bone marrow stromal cells upregulates vascular endothelial growth factor secretion: therapeutic applications. Leukemia. 2001; 15(12)1950–1961
  • Folkman J., Klagsbrun M. Angiogenic factors. Science. 1987; 235(4787)442–447
  • Folkman J. Role of angiogenesis in tumor growth and metastasis. Semin. Oncol. 2002; 29: 15–18, (6 Suppl 16)
  • Folkman J. Fundamental concepts of the angiogenic process. Curr Mol. Med. 2003; 3(7)643–651
  • Sledge G. W., Jr., Miller K. D. Angiogenesis and antiangiogenic therapy. Curr Probl. Cancer. 2002; 26(1)1–60
  • Ellis L. M., Liu W., Ahmad S. A., Fan F., Jung Y. D., Shaheen R. M., Reinmuth N. Overview of angiogenesis: Biologic implications for antiangiogenic therapy. Semin. Oncol. 2001; 28: 94–104, (5 suppl 16)
  • Cherrington J. M., Strawn L. M., Shawver L. K. New paradigms for the treatment of cancer: the role of anti-angiogenesis agents. Adv Cancer Res. 2000; 79: 1–38
  • Gasparini G., Brooks P. C., Biganzoli E., Vermeulen P. B., Bonoldi E., Dirix L. Y., Ranieri G., Miceli R., Cheresh D. A. Vascular integrin alpha(v)beta3: a new prognostic indicator in breast cancer. Clin Cancer Res. 1998; 4(11)2625–2634
  • Brooks P. C., Montgomery A. M., Rosenfeld M., Reisfeld R. A., Hu T., Klier G., Cheresh D. A. Integrin alpha v beta 3 antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels. Cell. 1994; 79(7)1157–1164
  • Eliceiri B. P., Cheresh D. A. The role of alphav integrins during angiogenesis: insights into potential mechanisms of action and clinical development. J Clin Invest. 1999; 103(9)1227–1230
  • Hynes R. O. A reevaluation of integrins as regulators of angiogenesis. Nat Med. 2002; 8(9)918–921
  • Hynes R. O., Lively J. C., McCarty J. H., Taverna D., Francis S. E., Hodivala-Dilke K., Xiao Q. The diverse roles of integrins and their ligands in angiogenesis. Cold Spring Harb. Symp Quant Biol. 2002; 67: 143–153
  • Stromblad S., Cheresh D. A. Integrins, angiogenesis and vascular cell survival. Chem Biol. 1996; 3(11)881–885
  • Varner J. A., Cheresh D. A. Tumor angiogenesis and the role of vascular cell integrin alphavbeta3. Important Adv Oncol. 1996; 69–87
  • Varner J. A. The role of vascular cell integrins alpha v beta 3 and alpha v beta 5 in angiogenesis. EXS 1997; 79: 361–390
  • Nikolopoulos S. N., Blaikie P., Yoshioka T., Guo W., Giancotti F. G. Integrin beta4 signaling promotes tumor angiogenesis. Cancer Cell. 2004; 6(5)471–483
  • Tucker G. C. Alpha v integrin inhibitors and cancer therapy. Curr Opin Investig Drugs. 2003; 4(6)722–731
  • Eliceiri B. P., Cheresh D. A. Role of alpha v integrins during angiogenesis. Cancer J. 2000; 6: S245–S249, (Suppl 3)
  • Kumar C. C., Armstrong L., Yin Z., Malkowski M., Maxwell E., Ling H., Yaremko B., Liu M., Varner J., Smith E. M., Neustadt B., Nechuta T. Targeting integrins alpha v beta 3 and alpha v beta 5 for blocking tumor-induced angiogenesis. Adv Exp Med Biol. 2000; 476: 169–180
  • Scatena M., Giachelli C. The alpha(v)beta3 integrin, NF-kappaB, osteoprotegerin endothelial cell survival pathway. Potential role in angiogenesis. Trends Cardiovasc Med. 2002; 12(2)83–88
  • Friedlander M., Theesfeld C. L., Sugita M., Fruttiger M., Thomas M. A., Chang S., Cheresh D. A. Involvement of integrins alpha v beta 3 and alpha v beta 5 in ocular neovascular diseases. Proc Natl Acad Sci U S A 1996; 93(18)9764–9769
  • Marshall J. F., Rutherford D. C., McCartney A. C., Mitjans F., Goodman S. L., Hart I. R. Alpha v beta 1 is a receptor for vitronectin and fibrinogen, and acts with alpha 5 beta 1 to mediate spreading on fibronectin. J Cell Sci. 1995; 108: 1227–1238, (Pt 3)
  • Breuss J. M., Gallo J., DeLisser H. M., Klimanskaya I. V., Folkesson H. G., Pittet J. F., Nishimura S. L., Aldape K., Landers D. V., Carpenter W. Expression of the beta 6 integrin subunit in development, neoplasia and tissue repair suggests a role in epithelial remodeling. J Cell Sci. 1995; 108: 2241–2251, (Pt 6)
  • Thomas G. J., Jones J., Speight P. M. Integrins and oral cancer. Oral Oncol. 1997; 33(6)381–388
  • Sipos B., Hahn D., Carceller A., Piulats J., Hedderich J., Kalthoff H., Goodman S. L., Kosmahl M., Kloppel G. Immunohistochemical screening for beta6-integrin subunit expression in adenocarcinomas using a novel monoclonal antibody reveals strong up-regulation in pancreatic ductal adenocarcinomas in vivo and in vitro. Histopathology. 2004; 45(3)226–236
  • Wang T., Li J., Goel H. L., Crockett K., Zhang J., Manes T., FitzGerald T. J., Languino L. R. A novel mechanism of prostate cancer progression mediated by the αvβ integrin. Proc Am Assoc Cancer Res. 2006; 47: LB-324
  • Munger J. S., Huang X., Kawakatsu H., Griffiths M. J., Dalton S. L., Wu J., Pittet J. F., Kaminski N., Garat C., Matthay M. A., Rifkin D. B., Sheppard D. The integrin alpha v beta 6 binds and activates latent TGF beta 1: a mechanism for regulating pulmonary inflammation and fibrosis. Cell. 1999; 96(3)319–328
  • Thomas G. J., Hart I. R., Speight P. M., Marshall J. F. Binding of TGF-beta1 latency-associated peptide (LAP) to alpha(v)beta6 integrin modulates behaviour of squamous carcinoma cells. Br J Cancer 2002; 87(8)859–867
  • Davidson B., Goldberg I., Reich R., Tell L., Dong H. P., Trope C. G., Risberg B., Kopolovic J. AlphaV- and beta1-integrin subunits are commonly expressed in malignant effusions from ovarian carcinoma patients. Gynecol Oncol. 2003; 90(2)248–257
  • Hibbs K., Skubitz K. M., Pambuccian S. E., Casey R. C., Burleson K. M., Oegema T. R., Jr., Thiele J. J., Grindle S. M., Bliss R. L., Skubitz A. P. Differential gene expression in ovarian carcinoma: identification of potential biomarkers. Am J Pathol 2004; 165(2)397–414
  • Kim S., Harris M., Varner J. A. Regulation of integrin alpha vbeta 3-mediated endothelial cell migration and angiogenesis by integrin alpha5beta1 and protein kinase A. J Biol Chem. 2000; 275(43)33920–33928
  • Reynolds L. E., Wyder L., Lively J. C., Taverna D., Robinson S. D., Huang X., Sheppard D., Hynes R. O., Hodivala-Dilke K. M. Enhanced pathological angiogenesis in mice lacking beta3 integrin or beta3 and beta5 integrins. Nat Med. 2002; 8(1)27–34
  • De S., Razorenova O., McCabe N. P., O'Toole T., Qin J., Byzova T. V. VEGF-integrin interplay controls tumor growth and vascularization. Proc Natl. Acad Sci U S A. 2005; 102(21)7589–7594
  • Eliceiri B. P. Integrin and growth factor receptor crosstalk. Circ Res. 2001; 89(12)1104–1110
  • Tucker G. C. Inhibitors of integrins. Curr Opin Pharmacol. 2002; 2(4)394–402
  • Taverna D., Moher H., Crowley D., Borsig L., Varki A., Hynes R. O. Increased primary tumor growth in mice null for beta3- or beta3/beta5-integrins or selectins. Proc Natl. Acad Sci U S A. 2004; 101(3)763–768
  • Cheresh D. A., Stupack D. G. Integrin-mediated death: an explanation of the integrin-knockout phenotype?. Nat. Med 2002; 8(3)193–194
  • Hsu M. Y., Shih D. T., Meier F. E., Van Belle P., Hsu J. Y., Elder D. E., Buck C. A., Herlyn M. Adenoviral gene transfer of beta3 integrin subunit induces conversion from radial to vertical growth phase in primary human melanoma. Am J Pathol 1998; 153(5)1435–1442
  • Kerr J. S., Mousa S. A., Slee A. M. Alpha(v)beta(3) integrin in angiogenesis and restenosis. Drug News Perspect. 2001; 14(3)143–150
  • Petitclerc E., Stromblad S., von Schalscha T. L., Mitjans F., Piulats J., Montgomery A. M., Cheresh D. A., Brooks P. C. Integrin alpha(v)beta3 promotes M21 melanoma growth in human skin by regulating tumor cell survival. Cancer Res. 1999; 59(11)2724–2730
  • Mitjans F., Meyer T., Fittschen C., Goodman S., Jonczyk A., Marshall J. F., Reyes G., Piulats J. In vivo therapy of malignant melanoma by means of antagonists of alphav integrins. Int J Cancer 2000; 87(5)716–723
  • Trikha M., Zhou Z., Nemeth J. A., Chen Q., Sharp C., Emmell E., Giles-Komar J., Nakada M. T. CNTO 95, a fully human monoclonal antibody that inhibits alphav integrins, has antitumor and antiangiogenic activity in vivo. Int J Cancer 2004; 110(3)326–335
  • Felding-Habermann B. Integrin adhesion receptors in tumor metastasis. Clin Exp. Metastasis 2003; 20(3)203–213
  • Rosano L., Spinella F., Di C. V., Dedhar S., Nicotra M. R., Natali P. G., Bagnato A. Integrin-linked kinase functions as a downstream mediator of endothelin-1 to promote invasive behavior in ovarian carcinoma. Mol Cancer Ther. 2006; 5(4)833–842
  • Westlin W. F. Integrins as targets of angiogenesis inhibition. Cancer J 2001; 7: S139–S143, (Suppl 3)
  • Leroy-Dudal J., Demeilliers C., Gallet O., Pauthe E., Dutoit S., Agniel R., Gauduchon P., Carreiras F. Transmigration of human ovarian adenocarcinoma cells through endothelial extracellular matrix involves alphav integrins and the participation of MMP2. Int J Cancer 2005; 114(4)531–543
  • Beck V., Herold H., Benge A., Luber B., Hutzler P., Tschesche H., Kessler H., Schmitt M., Geppert H. G., Reuning U. ADAM15 decreases integrin alphavbeta3/vitronectin-mediated ovarian cancer cell adhesion and motility in an RGD-dependent fashion. Int. J Biochem. Cell Biol. 2005; 37(3)590–603
  • Nabors L. B., Fiveash J. Treatment of adults with recurrent malignant glioma. Expert Rev Neurother. 2005; 5(4)509–514
  • Ding Q., Stewart J., Jr., Prince C. W., Chang P. L., Trikha M., Han X., Grammer J. R., Gladson C. L. Promotion of malignant astrocytoma cell migration by osteopontin expressed in the normal brain: differences in integrin signaling during cell adhesion to osteopontin versus vitronectin. Cancer Res. 2002; 62(18)5336–5343
  • Nemeth J. A., Cher M. L., Zhou Z., Mullins C., Bhagat S., Trikha M. Inhibition of alpha(v)beta3 integrin reduces angiogenesis, bone turnover, and tumor cell proliferation in experimental prostate cancer bone metastases. Clin Exp Metastasis. 2003; 20(5)413–420
  • Adams G. P., Schier R., McCall A. M., Simmons H. H., Horak E. M., Alpaugh R. K., Marks J. D., Weiner L. M. High affinity restricts the localization and tumor penetration of single-chain fv antibody molecules. Cancer Res. 2001; 61(12)4750–4755
  • Mikecz K. Vitaxin applied molecular evolution. Curr Opin Investig. Drugs 2000; 1(2)199–203
  • Faivre S. J., Chieze S., Marty M., Hammershaimb L., Pluda J., Lozahic S., Armand J. P., Raymond E. Safety profile and pharmacokinetic analysis of medi-522, a novel humanized monoclonal antibody that targets α vβ 3 integrin receptor, in patients with refractory solid tumors. Presented at: 2003 ASCO Annual Meeting, Abstract 832
  • Pizzolato J. F., Sharma S., Maki R., Krug M., Hammershaimb L., Pluda J. Phase I study of medi-522, an α vβ 3 integrin inhibitor, in patients (pts) with irinotecan-refractory colorectal cancer (CRC). Presented at: 2003 ASCO Annual Meeting, Abstract 983
  • Wilder R. L. Integrin alpha V beta 3 as a target for treatment of rheumatoid arthritis and related rheumatic diseases. Ann Rheum Dis. 2002; 61: ii96–ii99, (Suppl 2)
  • Hersey P., Sosman J., O'Day S., Richards J., Bedikian A., Gonzalez R., Sharfman W., Weber R., Logan T., Kirkwood J. M. A phase II, randomized, open-label study evaluating the antitumor activity of medi-522, a humanized monoclonal antibody directed against the human alpha v beta 3 (avb3) integrin, ± dacarbazine (DTIC) in patients with metastatic melanoma (MM). Presented at: 2005 ASCO Annual Meeting, Abstract 7507
  • Lode H. N., Moehler T., Xiang R., Jonczyk A., Gillies S. D., Cheresh D. A., Reisfeld R. A. Synergy between an antiangiogenic integrin alphav antagonist and an antibody-cytokine fusion protein eradicates spontaneous tumor metastases. Proc Natl Acad Sci U S A. 1999; 96(4)1591–1596
  • MacDonald T. J., Taga T., Shimada H., Tabrizi P., Zlokovic B. V., Cheresh D. A., Laug W. E. Preferential susceptibility of brain tumors to the antiangiogenic effects of an alpha(v) integrin antagonist. Neurosurgery. 2001; 48(1)151–157
  • Nabors L. B., Rosenfeld S. S., Mikkelsen T., Batchelor T., Olson J., Grossman S., Piantadosi S., Fisher J. D. A phase I trial of EMD 121974 for treatment of patients with recurrent malignant gliomas [Abstract TA-39]. Neuro.-Oncol. 2004; 6(4)379
  • Raguse J. D., Gath H. J., Bier J., Riess H., Oettle H. Cilengitide (EMD 121974) arrests the growth of a heavily pretreated highly vascularised head and neck tumour. Oral Oncol. 2004; 40(2)228–230
  • Smith J. W. Cilengitide Merck. Curr Opin Investig Drugs. 2003; 4(6)741–745
  • Chamberlain M. C. Treatment options for glioblastoma. Neurosurg Focus. 2006; 20(4)E2
  • Jayson G. C., Mullamitha S., Ton C., et al. Phase I study of CNTO 95, a fully human monoclonal antibody (mAb) to av integrins, in patients with solid tumors. Abstract 382. Ann Oncol. 2004; 15: iii102, (Suppl 3)
  • Coffey G. P., Stefanich E., Palmieri S., Eckert R., Padilla-Eagar J., Fielder P., Pippig S. In vitro internalization, intracellular transport and clearance of an anti-CD11a antibody (Raptiva™) by human T-cells. J Pharmacol Exp Ther. 2004; 279: 35903–35913
  • Ricart A., Liu G., Tolcher A., et al. A phase I dose-escalation study of anti-a5β1 integrin monoclonal antibody (M200) in patients with refractory solid tumors. Eur J Cancer 2004; 2(52), (suppl) (abstract 166)
  • Funahashi Y., Sugi N. H., Semba T., Yamamoto Y., Hamaoka S., Tsukahara-Tamai N., Ozawa Y., Tsuruoka A., Nara K., Takahashi K., Okabe T., Kamata J., Owa T., Ueda N., Haneda T., Yonaga M., Yoshimatsu K., Wakabayashi T. Sulfonamide derivative, E7820, is a unique angiogenesis inhibitor suppressing an expression of integrin alpha2 subunit on endothelium. Cancer Res. 2002; 62(21)6116–6123
  • Mita M. M., Mita A. C., Goldston M., Chu Q. S., Tolcher A. W., Ricart A., Desai P., Okereke C. S., Rowinsky E. K., Takimoto C. Pharmacokinetics (PK) and pharmcodynamics (PD) of E7820-an oral sulfonamide with novel, alpha-2 integrin mediated antiangiogenic properties: results of a phase I study. Presented at: 2005 ASCO Annual Meeting, Abstract 3082
  • Simon R., Freidlin B., Rubinstein L., Arbuck S. G., Collins J., Christian M. C. Accelerated titration designs for phase I clinical trials in oncology. J Natl. Cancer Inst. 1997; 89(15)1138–1147
  • Slaton J. W., Perrotte P., Inoue K., Dinney C. P., Fidler I. J. Interferon-alpha-mediated down-regulation of angiogenesis-related genes and therapy of bladder cancer are dependent on optimization of biological dose and schedule. Clin. Cancer Res. 1999; 5(10)2726–2734
  • Korn E. L., Arbuck S. G., Pluda J. M., Simon R., Kaplan R. S., Christian M. C. Clinical trial designs for cytostatic agents: are new approaches needed?. J Clin Oncol. 2001; 19(1)265–272
  • Eisenhauer E. A. Phase I and II trials of novel anti-cancer agents: endpoints, efficacy and existentialism. The Michel Clavel Lecture, held at the 10th NCI-EORTC Conference on New Drugs in Cancer Therapy, Amsterdam, 16-19 June 1998. Ann. Oncol 1998; 9(10)1047–1052
  • Parulekar W. R., Eisenhauer E. A. Phase I trial design for solid tumor studies of targeted, non-cytotoxic agents: theory and practice. J Natl. Cancer Inst. 2004; 96(13)990–997
  • Ellis L. M. Antiangiogenic therapy at a crossroads: clinical trial results and future directions. J Clin Oncol. 2003; 21: 281s–283s, (23 suppl)
  • Fiedler W., Mesters R., Tinnefeld H., Loges S., Staib P., Duhrsen U., Flasshove M., Ottmann O. G., Jung W., Cavalli F., Kuse R., Thomalla J., Serve H., O'Farrell A. M., Jacobs M., Brega N. M., Scigalla P., Hossfeld D. K., Berdel W. E. A phase 2 clinical study of SU5416 in patients with refractory acute myeloid leukemia. Blood. 2003; 102(8)2763–2767
  • McCarty M. F., Liu W., Fan F., Parikh A., Reimuth N., Stoeltzing O., Ellis L. M. Promises and pitfalls of anti-angiogenic therapy in clinical trials. Trends Mol. Med 2003; 9(2)53–58
  • Morgan B., Thomas A. L., Drevs J., Hennig J., Buchert M., Jivan A., Horsfield M. A., Mross K., Ball H. A., Lee L., Mietlowski W., Fuxuis S., Unger C., O'Byrne K., Henry A., Cherryman G. R., Laurent D., Dugan M., Marme D., Steward W. P. Dynamic contrast-enhanced magnetic resonance imaging as a biomarker for the pharmacological response of PTK787/ZK 222584, an inhibitor of the vascular endothelial growth factor receptor tyrosine kinases, in patients with advanced colorectal cancer and liver metastases: results from two phase I studies. J Clin Oncol. 2003; 21(21)3955–3964
  • Galbraith S. M., Maxwell R. J., Lodge M. A., Tozer G. M., Wilson J., Taylor N. J., Stirling J. J., Sena L., Padhani A. R., Rustin G. J. Combretastatin A4 phosphate has tumor antivascular activity in rat and man as demonstrated by dynamic magnetic resonance imaging. J Clin Oncol. 2003; 21(15)2831–2842
  • Hawighorst H., Weikel W., Knapstein P. G., Knopp M. V., Zuna I., Schonberg S. O., Vaupel P., van K. G. Angiogenic activity of cervical carcinoma: assessment by functional magnetic resonance imaging-based parameters and a histomorphological approach in correlation with disease outcome. Clin Cancer Res. 1998; 4(10)2305–2312
  • Pham C. D., Roberts T. P., van B. N., Melnyk O., Mann J., Ferrara N., Cohen R. L., Brasch R. C. Magnetic resonance imaging detects suppression of tumor vascular permeability after administration of antibody to vascular endothelial growth factor. Cancer Invest. 1998; 16(4)225–230
  • Sipkins D. A., Cheresh D. A., Kazemi M. R., Nevin L. M., Bednarski M. D., Li K. C. Detection of tumor angiogenesis in vivo by alphaVbeta3-targeted magnetic resonance imaging. Nat Med. 1998; 4(5)623–626
  • Abramovitch R., Dafni H., Smouha E., Benjamin L. E., Neeman M. In vivo prediction of vascular susceptibility to vascular susceptibility endothelial growth factor withdrawal: magnetic resonance imaging of C6 rat glioma in nude mice. Cancer Res. 1999; 59(19)5012–5016
  • Padhani A. R., Neeman M. Challenges for imaging angiogenesis. Br. J Radiol. 2001; 74(886)886–890
  • Jayson G. C., Zweit J., Jackson A., Mulatero C., Julyan P., Ranson M., Broughton L., Wagstaff J., Hakannson L., Groenewegen G., Bailey J., Smith N., Hastings D., Lawrance J., Haroon H., Ward T., McGown A. T., Tang M., Levitt D., Marreaud S., Lehmann F. F., Herold M., Zwierzina H. Molecular imaging and biological evaluation of HuMV833 anti-VEGF antibody: implications for trial design of antiangiogenic antibodies. J Natl Cancer Inst. 2002; 94(19)1484–1493
  • Evelhoch J. L. Key factors in the acquisition of contrast kinetic data for oncology. J Magn Reson Imaging. 1999; 10(3)254–259
  • Padhani A. R., Husband J. E. Dynamic contrast-enhanced MRI studies in oncology with an emphasis on quantification, validation and human studies. Clin Radiol. 2001; 56(8)607–620
  • Tofts P. S., Brix G., Buckley D. L., Evelhoch J. L., Henderson E., Knopp M. V., Larsson H. B., Lee T. Y., Mayr N. A., Parker G. J., Port R. E., Taylor J., Weisskoff R. M. Estimating kinetic parameters from dynamic contrast-enhanced T(1)-weighted MRI of a diffusable tracer: standardized quantities and symbols. J Magn Reson. Imaging 1999; 10(3)223–232
  • Jackson A., Haroon H., Zhu X. P., Li K. L., Thacker N. A., Jayson G. Breath-hold perfusion and permeability mapping of hepatic malignancies using magnetic resonance imaging and a first-pass leakage profile model. NMR Biomed. 2002; 15(2)164–173
  • Sotak C. H., Hees P. S., Huang H. N., Hung M. H., Krespan C. G., Raynolds S. A new perfluorocarbon for use in fluorine-19 magnetic resonance imaging and spectroscopy. Magn Reson Med. 1993; 29(2)188–195
  • Zhou J., Payen J. F., Wilson D. A., Traystman R. J., van Zijl P. C. Using the amide proton signals of intracellular proteins and peptides to detect pH effects in MRI. Nat Med. 2003; 9(8)1085–1090
  • Robinson S. P., Barton S. J., McSheehy P. M., Griffiths J. R. Nuclear magnetic resonance spectroscopy of cancer. Br J Radiol 1997; 70: S60–S69, (Spec No)
  • Beauregard D. A., Thelwall P. E., Chaplin D. J., Hill S. A., Adams G. E., Brindle K. M. Magnetic resonance imaging and spectroscopy of combretastatin A4 prodrug-induced disruption of tumour perfusion and energetic status. Br J Cancer 1998; 77(11)1761–1767
  • Shukla-Dave A., Zakina K. L., Raizer J., Hricak H., Koutcher J. A. MR spectroscopy of tumor physiology. Principles and Practice of Oncology:Updates. Lippincott Williams & Wilkins, Philadelphia 2003
  • Gupta N., Price P. M., Aboagye E. O. PET for in vivo pharmacokinetic and pharmacodynamic measurements. Eur J Cancer 2002; 38(16)2094–2107
  • Nakamoto Y., Zasadny K. R., Minn H., Wahl R. L. Reproducibility of common semi-quantitative parameters for evaluating lung cancer glucose metabolism with positron emission tomography using 2-deoxy-2-[18F]fluoro-D-glucose. Mol Imaging Biol. 2002; 4(2)171–178
  • Flamen P., Lerut T., Haustermans K., Van C. E., Mortelmans L. Position of positron emission tomography and other imaging diagnostic modalities in esophageal cancer. Q. J Nucl Med Mol. Imaging 2004; 48(2)96–108
  • Smith T. A. FDG uptake, tumour characteristics and response to therapy: a review. Nucl Med Commun. 1998; 19(2)97–105
  • Koh W. J., Rasey J. S., Evans M. L., Grierson J. R., Lewellen T. K., Graham M. M., Krohn K. A., Griffin T. W. Imaging of hypoxia in human tumors with [F-18]fluoromisonidazole. Int J Radiat Oncol Biol Phys 1992; 22(1)199–212
  • Wells P., Harte R. J., Price P. Positron emission tomography: a new investigational area for cancer research. Clin Oncol (R Coll. Radiol). 1996; 8(1)7–14
  • Bakir M. A., Eccles S., Babich J. W., Aftab N., Styles J., Dean C. J., Lambrecht R. M., Ott R. J. c-erbB2 protein overexpression in breast cancer as a target for PET using iodine-124-labeled monoclonal antibodies. J Nucl Med. 1992; 33(12)2154–2160
  • Collingridge D. R., Carroll V. A., Glaser M., Aboagye E. O., Osman S., Hutchinson O. C., Barthel H., Luthra S. K., Brady F., Bicknell R., Price P., Harris A. L. The development of [(124)I]iodinated-VG76e: a novel tracer for imaging vascular endothelial growth factor in vivo using positron emission tomography. Cancer Res. 2002; 62(20)5912–5919
  • Dehdashti F., Mortimer J. E., Siegel B. A., Griffeth L. K., Bonasera T. J., Fusselman M. J., Detert D. D., Cutler P. D., Katzenellenbogen J. A., Welch M. J. Positron tomographic assessment of estrogen receptors in breast cancer: comparison with FDG-PET and in vitro receptor assays. J Nucl. Med. 1995; 36(10)1766–1774
  • Chen X., Park R., Shahinian A. H., Tohme M., Khankaldyyan V., Bozorgzadeh M. H., Bading J. R., Moats R., Laug W. E., Conti P. S. 18F-labeled RGD peptide: initial evaluation for imaging brain tumor angiogenesis. Nucl Med Biol. 2004; 31(2)179–189
  • Beer A. J., Haubner R., Wolf I., Goebel M., Luderschmidt S., Niemeyer M., Grosu A. L., Martinez M. J., Wester H. J., Weber W. A., Schwaiger M. PET-based human dosimetry of 18F-galacto-RGD, a new radiotracer for imaging alpha v beta3 expression. J Nucl Med. 2006; 47(5)763–769
  • Haubner R., Weber W. A., Beer A. J., Vabuliene E., Reim D., Sarbia M., Becker K. F., Goebel M., Hein R., Wester H. J., Kessler H., Schwaiger M. Noninvasive visualization of the activated alphavbeta3 integrin in cancer patients by positron emission tomography and [18F]Galacto-RGD. PLoS. Med. 2005; 2(3)e70.
  • Beer A. J., Haubner R., Goebel M., Luderschmidt S., Spilker M. E., Wester H. J., Weber W. A., Schwaiger M. Biodistribution and pharmacokinetics of the alphavbeta3-selective tracer 18F-galacto-RGD in cancer patients. J Nucl. Med. 2005; 46(8)1333–1341
  • Cai W., Gambhir S., Chen X. Multimodality tumor imaging targeting integrin avβ3. Biotechniques 2005; 39: S6–S17, (Supplement)
  • Glaser M., Collingridge D. R., Aboagye E. O., Bouchier-Hayes L., Hutchinson O. C., Martin S. J., Price P., Brady F., Luthra S. K. Iodine-124 labelled annexin-V as a potential radiotracer to study apoptosis using positron emission tomography. Appl. Radiat. Isot. 2003; 58(1)55–62
  • Jain R. K., Duda D. G. Role of bone marrow-derived cells in tumor angiogenesis and treatment. Cancer Cell. 2003; 3(6)515–516
  • Rohan R. M., Fernandez A., Udagawa T., Yuan J., D'Amato R. J. Genetic heterogeneity of angiogenesis in mice. FASEB J. 2000; 14(7)871–876
  • Mancuso P., Burlini A., Pruneri G., Goldhirsch A., Martinelli G., Bertolini F. Resting and activated endothelial cells are increased in the peripheral blood of cancer patients. Blood. 2001; 97(11)3658–3661
  • Willett C. G., Boucher Y., di T. E., Duda D. G., Munn L. L., Tong R. T., Chung D. C., Sahani D. V., Kalva S. P., Kozin S. V., Mino M., Cohen K. S., Scadden D. T., Hartford A. C., Fischman A. J., Clark J. W., Ryan D. P., Zhu A. X., Blaszkowsky L. S., Chen H. X., Shellito P. C., Lauwers G. Y., Jain R. K. Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer. Nat Med. 2004; 10(2)145–147
  • Shaked Y., Bertolini F., Man S., Rogers M. S., Cervi D., Foutz T., Rawn K., Voskas D., Dumont D. J., Ben-David Y., Lawler J., Henkin J., Huber J., Hicklin D. J., D'Amato R. J., Kerbel R. S. Genetic heterogeneity of the vasculogenic phenotype parallels angiogenesis; Implications for cellular surrogate marker analysis of antiangiogenesis. Cancer Cell. 2005; 7(1)101–111
  • Lockhart A. C., Braun R. D., Yu D., Ross J. R., Dewhirst M. W., Klitzman B., Yuan F., Grichnik J. M., Proia A. D., Conway D. A., Mann G., Hurwitz H. I. A clinical model of dermal wound angiogenesis. Wound Repair Regen. 2003; 11(4)306–313
  • Lockhart A. C., Braun R. D., Yu D., Ross J. R., Dewhirst M. W., Humphrey J. S., Thompson S., Williams K. M., Klitzman B., Yuan F., Grichnik J. M., Proia A. D., Conway D. A., Hurwitz H. I. Reduction of wound angiogenesis in patients treated with BMS-275291, a broad spectrum matrix metalloproteinase inhibitor. Clin Cancer Res. 2003; 9(2)586–593
  • Fehm T., Sagalowsky A., Clifford E., Beitsch P., Saboorian H., Euhus D., Meng S., Morrison L., Tucker T., Lane N., Ghadimi B. M., Heselmeyer-Haddad K., Ried T., Rao C., Uhr J. Cytogenetic evidence that circulating epithelial cells in patients with carcinoma are malignant. Clin Cancer Res. 2002; 8(7)2073–2084
  • Cristofanilli M., Budd G. T., Ellis M. J., Stopeck A., Matera J., Miller M. C., Reuben J. M., Doyle G. V., Allard W. J., Terstappen L. W., Hayes D. F. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med. 2004; 351(8)781–791
  • Larson C. J., Moreno J. G., Pienta K. J., Gross S., Repollet M., O'hara S. M., Russell T., Terstappen L. W. Apoptosis of circulating tumor cells in prostate cancer patients. Cytometry A 2004; 62(1)46–53
  • Cohen S. J., Alpaugh R. K., Allard J., Cheng J. D., Gross S. T., Lewis N. L., Rogatko A., Sigurdson E., Weiner L. M., Meropol N. J. Isolation and characterization of circulating tumor cells in patients with colorectal cancer. Presented at: ASCO Annual Meeting 2003. Abstract 1186. Proc Am Soc Clin Oncol. 22: 295
  • Horton M. A., Taylor M. L., Arnett T. R., Helfrich M. H. Arg-Gly-Asp (RGD) peptides and the anti-vitronectin receptor antibody 23C6 inhibit dentine resorption and cell spreading by osteoclasts. Exp Cell Res. 1991; 195(2)368–375
  • Ross F. P., Chappel J., Alvarez J. I., Sander D., Butler W. T., Farach-Carson M. C., Mintz K. A., Robey P. G., Teitelbaum S. L., Cheresh D. A. Interactions between the bone matrix proteins osteopontin and bone sialoprotein and the osteoclast integrin alpha v beta 3 potentiate bone resorption. J Biol Chem. 1993; 268(13)9901–9907
  • Inoue M., Teitelbaum S. L., Hurter L., Hruska K., Seftor E., Hendrix M., Ross F. P. GM-CSF regulates expression of the functional integrins v3 and v5 in a reciprocal manner during osteoclastogenesis. J Bone Miner Res. 1995; 10: S163a
  • Delmas P. D., Eastell R., Garnero P., Seibel M. J., Stepan J. The use of biochemical markers of bone turnover in osteoporosis. Committee of Scientific Advisors of the International Osteoporosis Foundation. Osteoporos Int. 2000; 11: S2-17, (Suppl 6)
  • Stadler W. M., Ratain M. J. Development of target-based antineoplastic agents. Invest New Drugs. 2000; 18(1)7–16
  • Liu S. Y., Eary J. F., Petersdorf S. H., Martin P. J., Maloney D. G., Appelbaum F. R., Matthews D. C., Bush S. A., Durack L. D., Fisher D. R., Gooley T. A., Bernstein I. D., Press O. W. Follow-up of relapsed B-cell lymphoma patients treated with iodine-131-labeled anti-CD20 antibody and autologous stem-cell rescue. J Clin Oncol. 1998; 16(10)3270–3278
  • Zee B., Melnychuk D., Dancey J., Eisenhauer E. Multinomial phase II cancer trials incorporating response and early progression. J Biopharm Stat. 1999; 9(2)351–363
  • Casper E. S., Green M. R., Kelsen D. P., Heelan R. T., Brown T. D., Flombaum C. D., Trochanowski B., Tarassoff P. G. Phase II trial of gemcitabine (2,2′-difluorodeoxycytidine) in patients with adenocarcinoma of the pancreas. Invest New Drugs. 1994; 12(1)29–34
  • Burris H. A., III, Moore M. J., Andersen J., Green M. R., Rothenberg M. L., Modiano M. R., Cripps M. C., Portenoy R. K., Storniolo A. M., Tarassoff P., Nelson R., Dorr F. A., Stephens C. D., Von Hoff D. D. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol. 1997; 15(6)2403–2413
  • Simon R., Wittes R. E., Ellenberg S. S. Randomized phase II clinical trials. Cancer Treat Rep. 1985; 69(12)1375–1381
  • Leyland-Jones B. Maximizing the response to Herceptin therapy through optimal use and patient selection. Anticancer Drugs. 2001; 12: S11–S17, (Suppl 4)
  • Leyland-Jones B. Trastuzumab: hopes and realities. Lancet Oncol. 2002; 3(3)137–144
  • Bilous M., Dowsett M., Hanna W., Isola J., Lebeau A., Moreno A., Penault-Llorca F., Ruschoff J., Tomasic G., van D. Current V. perspectives on HER2 testing: a review of national testing guidelines. Mod. Pathol. 2003; 16(2)173–182
  • Yamauchi H., Stearns V., Hayes D. F. When is a tumor marker ready for prime time? A case study of c-erbB-2 as a predictive factor in breast cancer. J Clin Oncol 2001; 19(8)2334–2356
  • Hanna W. M., Kahn H. J., Pienkowska M., Blondal J., Seth A., Marks A. Defining a test for HER-2/neu evaluation in breast cancer in the diagnostic setting. Mod Pathol. 2001; 14(7)677–685
  • Tsongalis G. J., Ried A. Jr. HER2: the neu prognostic marker for breast cancer. Crit Rev Clin Lab Sci. 2001; 38(2)167–182
  • Sledge G. W., Jr. Vascular endothelial growth factor in breast cancer: biologic and therapeutic aspects. Semin Oncol. 2002; 29: 104–110, (3 Suppl 11)
  • Kuenen B. C., Tabernero J., Baselga J., Cavalli F., Pfanner E., Conte P. F., Seeber S., Madhusudan S., Deplanque G., Huisman H., Scigalla P., Hoekman K., Harris A. L. Efficacy and toxicity of the angiogenesis inhibitor SU5416 as a single agent in patients with advanced renal cell carcinoma, melanoma, and soft tissue sarcoma. Clin Cancer Res. 2003; 9(5)1648–1655
  • Trikha M., Zhou Z., Nemeth J. A., Chen Q., Sharp C., Emmell E., Giles-Komar J., Nakada M. T. CNTO 95, a fully human monoclonal antibody that inhibits alphav integrins, has antitumor and antiangiogenic activity in vivo. Int J Cancer 2004; 110(3)326–335
  • Chen H. X. Expanding the clinical development of bevacizumab. Oncologist 2004; 9: 27–35, (Suppl 1)
  • Gerber H. P., Ferrara N. Pharmacology and pharmacodynamics of bevacizumab as monotherapy or in combination with cytotoxic therapy in preclinical studies. Cancer Res. 2005; 65(3)671–680
  • Chen H. X., Gore-Langton R. E., Cheson B. D. Clinical trials referral resource: Current clinical trials of the anti-VEGF monoclonal antibody bevacizumab. Oncology (Huntingt) 2001; 15(8)1017, 1020, 1023, 1026
  • Margolin K., Gordon M. S., Holmgren E., Gaudreault J., Novotny W., Fyfe G., Adelman D., Stalter S., Breed J. Phase Ib trial of intravenous recombinant humanized monoclonal antibody to vascular endothelial growth factor in combination with chemotherapy in patients with advanced cancer: pharmacologic and long-term safety data. J Clin Oncol. 2001; 19(3)851–856
  • Wildiers H., Guetens G., De B. G., Verbeken E., Landuyt B., Landuyt W., de Bruijn E. A., van Oosterom A. T. Effect of antivascular endothelial growth factor treatment on the intratumoral uptake of CPT-11. Br J Cancer 2003; 88(12)1979–1986
  • Genentech I. Avastin™ (bevacizumab). US prescribing information. 2005. South San Francisco, CA 2005
  • DeNardo S. J., Burke P. A., Leigh B. R., O'Donnell R. T., Miers L. A., Kroger L. A., Goodman S. L., Matzku S., Jonczyk A., Lamborn K. R., DeNardo G. L. Neovascular targeting with cyclic RGD peptide (cRGDf-ACHA) to enhance delivery of radioimmunotherapy. Cancer Biother Radiopharm 2000; 15(1)71–79
  • Burke P. A., DeNardo S. J., Miers L. A., Lamborn K. R., Matzku S., DeNardo G. L. Cilengitide targeting of alpha(v)beta(3) integrin receptor synergizes with radioimmunotherapy to increase efficacy and apoptosis in breast cancer xenografts. Cancer Res. 2002; 62(15)4263–4272
  • Li L., Wartchow C. A., Danthi S. N., Shen Z., Dechene N., Pease J., Choi H. S., Doede T., Chu P., Ning S., Lee D. Y., Bednarski M. D., Knox S. J. A novel antiangiogenesis therapy using an integrin antagonist or anti-Flk-1 antibody coated 90Y-labeled nanoparticles. Int J Radiat Oncol Biol Phys 2004; 58(4)1215–1227
  • Fahr A., Muller K., Nahde T., Muller R., Brusselbach S. A new colloidal lipidic system for gene therapy. J Liposome Res. 2002; 12(1-2)37–44
  • Reynolds A. R., Moein M. S., Hodivala-Dilke K. Nanoparticle-mediated gene delivery to tumour neovasculature. Trends Mol Med. 2003; 9(1)2–4
  • McQuade P., Knight L. C. Radiopharmaceuticals for targeting the angiogenesis marker alpha(v)beta(3). Q J Nucl Med. 2003; 47(3)209–220

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.