PDK1 and neoplasm: Copper activates a series of cancer-related kinase-signaling pathways, including the RAS-RAF-MEK-ERK1/2 and PI3K-PDK1-AKT pathways.115,116 Specifically, copper acts as a cofactor of MEK1/2 can allosterically enhance its capability to phosphorylate ERK1/2 in a dose-dependent manner, which further promotes the expression of c-myc, c-fos, and c-jun in the nucleus to regulate tumor growth.117–119 This copper-dependent vulnerability has been demonstrated in tumor models with BRAF or KRAS mutations.