CDK12 and melanoma: While CDK12 facilitates activation of ERBB–PI3K–AKT and WNT signaling pathways in HER2-positive breast cancer through promoting transcription of an RTK adaptor IRS-1 and WNT ligands genes, respectively (33), it is constitutively activated by the hyperactive RAS–BRAF–MEK1/2–ERK1/2 signaling pathway in BRAF-mutated melanoma (34).