The inhibition of caspase enzymatic activity by zVAD-fmk in human renal cell carcinoma A498 cells, demonstrated that metformin-induced apoptosis facilitated degradation of the cellular caspase 8 (FLICE)-like inhibitory protein and activated procaspase-8 through a caspase-dependent pathway (Jang et al., 2018). Here, CASP8 is linked to hereditary clear cell renal cell carcinoma.