The Dynamics of the Cell Signaling Network; Implications for Targeted Therapies

摘要: Molecular targeted therapies against signaling molecules that are active in ­cancer have shown only incomplete and temporary clinical benefit when used as single agents. One explanation for the limited is extracellular signals transmitted through a network of proteins rather than hierarchical pathways; inhibition component insufficient to dramatic effects on treatment cancer since biological outcome propagated inherently more resistant perturbations. In this chapter, we discuss major mechanisms resistance therapeutics using alterations cell network. We present specific examples redundant (intrinsic) compensatory (acquired) leading resistance. These include (1) mutation downstream effector rendering an upstream activator ineffective (2) presence pathways regulating growth well including (3) upregulation second pathway which substitutes pathway, (4) loss feedback control inhibiting facilitates activation components pathway. also general implications design effective drug treatments.