In response to maximum tolerated doses of chemotherapy, Chan et al. found that cancer-associated fibroblasts are activated through increased activity of signal transducer and activator of transcription 1 (STAT1) and nuclear factor-κB (NF-κB), leading to elevated levels and release of ELR+ chemokines. These chemokines bind to C-X-C chemokine receptor type 2 (CXCR2) on tumour cell surfaces causing a phenotypic shift to tumour-initiating cells and promoting aggressive tumour behaviours. Metronomic chemotherapy regimens mostly prevented this effect, suggesting that long-term, low-dose chemotherapy might be more effective than high-dose chemotherapy in driving antitumour activity.
References
Chan, T-S. et al. Metronomic chemotherapy prevents therapy-induced stromal activation and induction of tumor-initiating cells. J. Exp. Med. http://dx.doi.org/10.1084/jem.20151665 (2016)
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Dart, A. Less is more. Nat Rev Cancer 17, 3 (2017). https://doi.org/10.1038/nrc.2016.151
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DOI: https://doi.org/10.1038/nrc.2016.151
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