SMAD3 and cancer: However, as we pointed out previously, the first neighbours of differentially expressed proteins often have high degree and/or high betweenness parameters, thereby their pharmacological targeting could produce more side effects.32,33 Accordingly, these proteins are rarely found in any cancer type mutated or differential expressed, probably because most of them (such as SMAD3, GSK3β, ERK1) are multi-functional and have a central position.