Regorafenib, a multikinase inhibitor with anti-angiogenic activity, shows efficacy in patients with treatment-refractory metastatic colorectal cancer (mCRC). However, modest efficacy in an unselected patient population indicates that better predictive biomarkers of response to regorafenib are needed for appropriate patient selection. In a prospective phase II study of patients (n = 27) with mutant RAS mCRC, Khan et al. found that early (day 15 after treatment) imaging with dynamic contrast-enhanced (DCE) MRI, to establish changes in tumour volume, predicted response and long-term outcomes to regorafenib therapy. Reduced tumour vasculature after treatment was confirmed using tissue biopsies and was associated with a marked reduction in circulating tumour DNA (ctDNA) that, if sustained for 8 weeks, led to even better patient outcomes. Thus, combining DCE-MRI with ctDNA as biomarkers of response to regorafenib might improve patient selection.