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Cancer Cell. 2014 Nov 10;26(5):605-22. doi: 10.1016/j.ccell.2014.10.006. Epub 2014 Nov 10.

Antiangiogenesis strategies revisited: from starving tumors to alleviating hypoxia.

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Edwin L. Steele Laboratory for Tumor Biology, Department of Radiation Oncology, Harvard Medical School and Massachusetts General Hospital, 100 Blossom Street, Cox 7, Boston, MA 02114, USA. Electronic address:


Ten antiangiogenic drugs targeting VEGF or its receptors are approved for cancer treatment. However, these agents, intended to block tumors' blood supply, may cause hypoxia, which may fuel tumor progression and treatment resistance. Emerging clinical data suggest that patients whose tumor perfusion or oxygenation increases in response to these agents may actually survive longer. Hence, strategies aimed at alleviating tumor hypoxia while improving perfusion may enhance the outcome of radiotherapy, chemotherapy, and immunotherapy. Here I summarize lessons learned from preclinical and clinical studies over the past decade and propose strategies for improving antiangiogenic therapy outcomes for malignant and nonmalignant diseases.

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