This leads to a RAS dependence, and as a result, most tumours with class III mutations harbour alterations in RAS genes, their activators such as receptor tyrosine kinases (RTKs) or negative regulators, such as NF1.13,22,23 Similarly, BRAFV600E-selective inhibitors with a binding preference for RAF proteins in their monomeric state, including dabrafenib, can also cause paradoxical MEK/ERK pathway activation in the context of active RAS.20 This evidence concerns the gene RAF1 and neoplasm.