These dualities in the functions of specific isoforms appears to rely on complex and mechanistically still unclear bidirectional interplay of S100 isoforms with key cellular factors and cancer drivers, e.g., p53 [84], Wnt/β-catenin [85], p38 Mitogen-Activated Protein Kinases (p38 MAPK) [86], ERK [87], AKT [88], p21 [89] or NFκB [90], among others. This evidence concerns the gene S100B and cancer.