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.