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Angiogenesis

High and lows

Nature Reviews Cancer volume 3, page 8 (2003)Cite this article

Bocci et al. exposed human tumour cells, fibroblasts and endothelial cells to daily low concentrations of chemotherapeutic drugs for up to 6 days — analogous to the protracted metronomic protocols used in patients. They observed specific inhibition of endothelial-cell proliferation with taxanes and cyclophosphamide after 6 days, but not after 24 hours, using concentrations of 10–100 pM and 1–100 nM, respectively. By contrast, normal fibroblasts and breast cancer cell lines were not affected. Not all drugs showed this differential effect — doxorubicin had similar antiproliferative activity against both endothelial cells and breast cancer cells. In addition, the authors observed that treated endothelial cells had a higher level of apoptosis than the cancer cell lines or fibroblasts.

So, prolonged exposure times, once an effective dose of drug has been reached, are crucial for cell kill in high-time chemotherapy regimens and might be selective for endothelial cells. This type of schedule might create an anti-angiogenic therapeutic window, and could be used to treat tumours that are resistant to the very drugs that are used for low-dose chemotherapy or to decrease host toxicity without reducing efficacy. It remains to be seen whether other types of normal cells are also highly sensitive to metronomic dosing.

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ORIGINAL RESEARCH PAPER

  1. Bocci, G. et al. Protracted low-dose effects on human endothelial cell proliferation and survival in vitro reveal a selective antiangiogenic window for various chemotherapeutic drugs. Cancer Res. 62, 6938–6943 (2002)

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  1. Ezzie Hutchinson
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Hutchinson, E. High and lows. Nat Rev Cancer 3, 8 (2003). https://doi.org/10.1038/nrc981

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  • DOI: https://doi.org/10.1038/nrc981

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