To test whether dependency on WNT signalling was maintained in CRC cell populations that developed multiple heterogeneous mechanisms of targeted drug resistance, we first generated populations of cells resistant to the BRAF inhibitor dabrafenib, alone or in combination with the anti-EGFR monoclonal antibody cetuximab (Supplementary Fig. 1a, b; Supplementary Table 1), as combination regimens have shown promising activity in BRAF-mutated metastatic colorectal cancer (mCRC) patients31. Here, BRAF is linked to colorectal carcinoma.