MYC and cancer: Constitutive activation of ERK signaling in many cancers is caused by factors such as overexpression or mutation in receptor tyrosine kinases, Ras and Raf mutations, sustained autocrine or paracrine production of activating ligands, and the direct amplification or deregulation of its transcription factor targets, such as MYC, HIF-α, activator protein 1 and signal transducers and activators of transcription [53].