In this commentary we discuss results from our recent study[11], including a novel tumour suppressive pathway activated by excessive ERK1/2 signalling involving expression of the CDKI p57KIP2, encoded by CDKN1C. p57KIP2 expression is strongly linked to the magnitude of ERK1/2 signalling and drives cell cycle arrest when MEKi is withdrawn from MEKi-resistant cells with BRAFV600E amplification[11]. This evidence concerns the gene CDKN1C and neoplasm.