PIK3CA and cancer: Notably, numerous studies found that BETi inactivate transcriptional programmes involved in RTK signalling exclusively in sensitive cells.88,94–98 Supporting this concept, the activation of PI3K and ERK/MAPK signalling cascades appears to dictate intrinsic resistance to BETi in multiple types of cancer (Fig. 2).88,97–100 This was clearly demonstrated through ectopic expression of constitutively active downstream effectors of these pathways, including AKT, KRAS and BRAF, all of whom conferred resistance to BETi.99,101