MAPK1 and cancer: In the context of positive metalloallostery, Cu directly binds to MEK1 and MEK2 kinases and enhances their ability to phosphorylate ERK1 and ERK2 in a dose-dependent manner, stimulating the RAF–MEK–ERK signaling cascade, and ultimately, further promoting tumor proliferation [90]; this makes Cu an attractive target as this signaling cascade is one of the best-defined axes that promote cell proliferation and it is abnormal in most human cancers.