A recent circulating tumour DNA sequencing analysis from mCRC patients has revealed five novel mutations on exon 19 of PIK3CA (K944N, V955I, F930S, V955G and K966E) that may potentially drive resistance to cetuximab via EGFR-mediated activation of the PI3K/PKB signalling pathway, suggesting that combined regimens of PI3K/mTOR inhibitors (PP242 and NVP-BEZ235) with anti-EGFR therapy may be beneficial to overcome the resistance (Xu et al., 2017). The gene discussed is EGFR; the disease is neoplasm.