Steeg replies
I appreciate the thoughtful comments of Folkman, Kieran and Heymach. The landmark work of Folkman and his colleagues in the field of antiangiogenesis has, of course, revolutionized how we all think about cancer and has provided the foundation for a generation of scientists to think about new ways to approach therapy and prevention of this disease. The extraordinary recent report12 of an antiangiogenic approach providing a survival advantage of several months is testament, in itself, of the tangible merit of this approach.
My News and Views discussed a paper linking low oxygen supply and induction of invasion. These newer findings may also merit consideration. It is the discussion of potential wrinkles in data that propels us to think about new ideas, such as combinations of antiangiogenic and anti-invasive agents. Such new ideas could turn the recent survival advantage in the colorectal carcinoma trial from several months to several years. It has, of course, been the remarkable work of Folkman and his colleagues that has inspired us all and given us the opportunity to address these interesting issues.
See “Angiogenesis inhibitors and hypoxia” by Kieran et al.
References
Steeg, P.S. Angiogenesis inhibitors: motivators of metastasis? Nat. Med. 9, 822–823 (2003).
Pennacchietti, S. et al. Hypoxia promotes invasive growth by transcriptional activation of the met protooncogene. Cancer Cell 3, 347–361 (2003).
Bottaro, D.P. & Liotta, L.A. Out of air is not out of action. Nature 423, 593–595 (2003).
Shaheen, R.M. et al. Antiangiogenic therapy targeting the tyrosine kinase receptor for vascular endothelial growth factor receptor inhibits the growth of colon cancer liver metastases and induces tumor and endothelial cell apoptosis. Cancer Res. 59, 5412–5416 (1999).
Drevs, J. et al. Effects of PTK787/ZK222584, a specific inhibitor of vascular endothelial growth factor tyrosine kinases, on primary tumor metastasis, vessel density, and blood flow in a murine renal cell carcinoma model. Cancer Res. 60, 4819–4824 (2000).
Inoue, K. et al. Frequent administration of angiogenesis inhibitor TNP-470 (AGM-1470) at an optimal biological dose inhibits tumor growth and metastasis of metastatic human transitional cell carcinoma in the urinary bladder. Clin. Cancer Res. 8, 2389–2398 (2002).
Sauter, B.V. et al. Adenovirus-mediated gene transfer of endostatin in vivo results in high level of transgene expression and inhibition of tumor growth and metastases. Proc. Natl. Acad. Sci. USA 97, 4802–4807 (2002).
Wang, L. et al. Mechanism of interferon alpha on inhibition of metastasis and angiogenesis of hepatocellular carcinoma after curative resection in nude mice. J. Gastrointest. Surg. 7, 587–594 (2003).
Kaban, L. et al. Antiangiogenic therapy with interferon alpha for giant cell lesions of the jaws. J. Oral Maxillofac. Surg. 60, 1103–1111 (2002).
Holmgren, L., O'Reilly, M.S. & Folkman, J. Dormancy of micrometastases: balanced proliferation and apoptosis in the presence of angiogenesis suppression. Nat. Med. 1, 149–153 (1995).
Camphausen, K. et al. Radiation therapy to a primary tumor accelerates metastatic growth in mice. Cancer Res. 61, 2207–2211 (2001).
Weber, D. et al. Thalidomide alone or with dexamethasone for previously untreated multiple myeloma. J. Clin. Oncol. 21, 16–19 (2003).
Steinbach, G. et al. The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. N. Engl. J. Med. 342, 1946–1952 (2000).
Yu, J., Rak, J., Coomber, B., Hicklin, D. & Kerbel, R. Effect of tumor response to p53 status on tumor response to antiangiogenic therapy. Science 295, 1526–1528 (2002).
Browder, T. et al. Antiangiogenic therapy and p53. Science 297, 471 (2002).
Mabjeesh, N.J. et al. 2ME2 inhibits tumor growth and angiogenesis by disrupting microtubules and dysregulating HIF. Cancer Cell 3, 363–375 (2003).
Folkman, J. & Kalluri, R. Tumor angiogenesis. in Cancer Medicine, 6th edn. (eds. Kufe, D.W. et al.) 161–194 (B.C. Decker, Hamilton, Ontario, 2003).
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Steeg, P. Reply to “Angiogenesis inhibitors and hypoxia”. Nat Med 9, 1104 (2003). https://doi.org/10.1038/nm0903-1104b
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DOI: https://doi.org/10.1038/nm0903-1104b
