Anti-angiogenic therapy, predominantly with the anti-VEGF antibody bevacizumab, has not been shown to improve the survival of patients with breast cancer. 70% of patients with this disease are overweight or obese; now, data from 99 patients treated with bevacizumab indicate that a high BMI (≥25) is associated with tumours that are typically larger at diagnosis, hypovascular, hypoxic, and insensitive to bevacizumab. Interestingly, patients with a high BMI had high circulating levels of IL-6 and FGF2. In obese mice with breast cancer, elevated expression of FGF2 or IL-6 by adipocytes and other cells of the tumour microenvironment was likewise associated with resistance to anti-VEGF therapy, which could be overcome through pharmacological antagonism of the FGF2 or IL-6 axes.
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Incio, J. et al. Obesity promotes resistance to anti-VEGF therapy in breast cancer by up-regulating IL-6 and potentially FGF-2. Sci. Transl Med. 10, eaag0945 (2018)
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Killock, D. Obesity associated with resistance to anti-angiogenic therapy. Nat Rev Clin Oncol 15, 344 (2018). https://doi.org/10.1038/s41571-018-0011-5
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DOI: https://doi.org/10.1038/s41571-018-0011-5