In an early stage, SMYD3 can mediate the epigenetic response to stressors (i.e., HSP90, RPB1); upon persistent stress stimulation, it can interact with upstream stress sensors (i.e., HSP90 and ATM), while in a later stage, it can interact with downstream cancer-related effectors (i.e., AKT1, VGFR1, p53, MAP3K2), triggering specific downstream cascades that promote cancer cell proliferation and cancer progression [1], [104]. This evidence concerns the gene POLR2A and cancer.