Anti-angiogenic therapy was proposed in 1971 as a means to treat solid tumors and in 1976 as a method of cancer prevention. Here we propose that this form of therapy, judiciously applied, can normalize the tumor vasculature and improve the delivery of therapeutics.
This is a preview of subscription content, access via your institution
Relevant articles
Open Access articles citing this article.
-
Development of a dual energy CT based model to assess response to treatment in patients with high grade serous ovarian cancer: a pilot cohort study
Cancer Imaging Open Access 15 June 2023
-
Efficacy and safety of EGFR-TKIs in combination with angiogenesis inhibitors as first-line therapy for advanced EGFR-mutant non-small-cell lung cancer: a systematic review and meta-analysis
BMC Pulmonary Medicine Open Access 14 June 2023
-
Angiogenic signaling pathways and anti-angiogenic therapy for cancer
Signal Transduction and Targeted Therapy Open Access 11 May 2023
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
References
Jain, R.K. The next frontier of molecular medicine: delivery of therapeutics. Nature Med. 4, 655–657 (1998).
Browder, T. et al. Anti-angiogenic scheduling of chemotherapy improves efficacy against experimental drug–resistant cancer. Cancer Res. 60, 1878–1886 (2000).
Klement, G. et al. Continuous low-dose therapy with vinblastine and VEGF receptor-2 antibody induces sustained tumor regression without overt toxicity. J. Clin. Invest. 105, R15–24 (2000).
Folkman, J. in Harrison's Textbook of Internal Medicine, 15th ed. (eds Braunwald, E. et al.) 517–530 (McGraw-Hill, New York, 2001).
Carmeliet, P. & Jain, R.K. Angiogenesis in cancer and other diseases. Nature 407, 249–257 (2000).
Teicher, B.A. A systems approach to cancer therapy. Cancer Metastasis Rev. 15, 247–272 (1996).
Kozin, S.V. et al. VEGF receptor-2 blocking antibody potentiates radiation-induced long-term control of human tumor xenografts. Cancer Res. 61, 39–44 (2001).
Jain, R.K. Barriers to drug delivery in solid tumors. Sci. Am. 271, 58–65 (1994).
Baish, J. et al. Fractals and cancer. Cancer Res. 60, 3683–3688 (2000).
Tsuzuki, Y. et al. VEGF modulation by targeting HIF-1α→HRE→VEGF cascade differentially regulates vascular response and growth rate in tumors. Cancer Research 60, 6248–6252 (2000).
Yuan F., et al. Time-dependent vascular regression and permeability changes in established human tumor xenografts induced by an anti-VEGF/VPF antibody. Proc. Natl. Acad. Sci. USA 93, 14765–14770 (1996).
Kadambi, A. et al. Vascular endothelial growth factor (VEGF)–C differentially affects tumor vascular function and leukocyte recruitment. Cancer Res. 61, 2404–2408 (2001).
Lee, C.G. et al. Anti-VEGF treatment augments tumor radiation response under normoxic or hypoxic conditions. Cancer Res. 60, 5565–5570 (2000).
Hansen-Algenstaedt, N. et al. Tumor oxygenation during VEGFR-2 blockade, hormone ablation, and chemotherapy. Cancer Res. 60, 4556–4560 (2000).
Jain, R.K. et al. Endothelial cell death, angiogenesis, and microvascular function following castration in an androgen-dependent tumor: Role of VEGF. Proc. Natl. Acad. Sci. USA 95, 10820–10825 (1998).
Uehara, H., Kim, S.J., Karashima, T., Zheng, L. & Fidler, I.J. Blockade of PDGF-R signaling by STI571 inhibits angiogenesis and growth of human prostate cancer cells in the bone of nude mice. Abstract 2192. American Association for Cancer Research 92nd Annual Meeting, New Orleans (April 2001).
Viloria-Petit, A. et al. Acquired resistance to the antitumor effect of epidermal growth factor receptor-blocking antibodies in vivo: a role for altered tumor angiogenesis. Cancer Res. 61, 5090–5101 (2001).
Benjamin, L.E., Golijanin, D., Itin, A., Pode, D. & Keshet E. Selective ablation of immature blood vessels in established human tumors follows vascular endothelial growth factor withdrawal. J. Clin. Invest. 103, 159–165 (1999).
Fidler, I.J. Angiogenic heterogeneity: regulation of neoplastic angiogenesis by the organ microenvironment. J. Natl. Cancer Inst. 93, 1040–1041 (2001).
Ruoslahti, E. Targeting tumor vasculature with homing peptides from phage display. Semin. Cancer Biol. 10, 435–442 (2000).
Thorpe, P.E. & Ran, S. Tumor infarction by targeting tissue factor to tumor vasculature. Cancer J. Sci. Am. 6 Suppl 3, S237–244 (2000).
Gasparini, G. et al. Vascular integrin α(v)β3: a new prognostic indicator in breast cancer. Clin. Cancer Res. 4, 2625–2634 (1998).
St Croix, B. et al. Genes expressed in human tumor endothelium. Science 289, 1197–1202 (2000).
Griffon-Etienne, G. et al. Taxane-induced apoptosis decompresses blood vessels and lowers interstitial fluid pressure in solid tumors: clinical implications. Cancer Res. 59, 3776–3782 (1999).
Murata, R., Nishimura, Y. & Hiraoka, M. An antiangiogenic agent (TNP-470) inhibited reoxygenation during fractionated radiotherapy of murine mammary carcinoma. Int. J. Radiat. Oncol. Biol. Phys. 37, 1107–1113 (1997).
Ma, J. et al. Pharmacodynamic-mediated reduction of Temozolomide tumor concentrations by the angiogenesis inhibitor TNP-470. Cancer Res. 61, 5491–5498 (2001).
Gullino, P.M. Angiogenesis and oncogenesis. J. Natl. Cancer Inst. 61, 639–643 (1978).
Milosevic, M. et al. Interstitial fluid pressure predicts survival in patients with cervix cancer independent of clinical prognostic factors and tumor oxygen measurements. Cancer Res. 61, 6400–6405 (2001).
Acknowledgements
We thank the members of the Steele Laboratory, especially B. Fenton, E. diTomaso and L. Munn, as well as I.J. Fidler, J. Folkman, R. Kerbel, J. Loeffler, J. Samson, B. Seed, H. Suit, J. Tatum and B. Teicher for helpful discussions.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Jain, R. Normalizing tumor vasculature with anti-angiogenic therapy: A new paradigm for combination therapy. Nat Med 7, 987–989 (2001). https://doi.org/10.1038/nm0901-987
Issue Date:
DOI: https://doi.org/10.1038/nm0901-987
This article is cited by
-
Image-based modeling of vascular organization to evaluate anti-angiogenic therapy
Biology Direct (2023)
-
Efficacy and safety of EGFR-TKIs in combination with angiogenesis inhibitors as first-line therapy for advanced EGFR-mutant non-small-cell lung cancer: a systematic review and meta-analysis
BMC Pulmonary Medicine (2023)
-
Development of a dual energy CT based model to assess response to treatment in patients with high grade serous ovarian cancer: a pilot cohort study
Cancer Imaging (2023)
-
Mesoporous nanodrug delivery system: a powerful tool for a new paradigm of remodeling of the tumor microenvironment
Journal of Nanobiotechnology (2023)
-
Hypoxic microenvironment in cancer: molecular mechanisms and therapeutic interventions
Signal Transduction and Targeted Therapy (2023)