Artificial Signal Transduction Therapy: A Futuristic Approach to Disease Treatment

The most basic functions of the cell such as proliferation, differentiation, metabolism and apoptosis are dependent on signal transduction pathways that determine the response of the cell to various environmental signals [1]. These pathways generally begin by the binding of a ligand to an extracellular receptor, which triggers an intracellular signal cascade. The propagation of the signal within the cell is mediated by various protein–protein interactions, in which enzymes activate or deactivate one another with high specificity. Because numerous diseases such as cancer are associated with dysregulation of these networks, much effort has been devoted to developing drugs that disrupt protein–protein interactions or inhibit enzymes that are involved in abnormal cell signaling pathways [2,3]. Herceptin and gleevec [4], for example, are well-known anticancer drugs that inhibit the signaling pathways of receptor tyrosine kinases (RTKs) in different ways. The first is an antibody-based drug that binds the extracellular domain of HER-2, a member of the EGFRs family. It disrupts dimerization of HER-2 with neighboring HER receptors and consequently prevents the activation of intracellular kinases. The second drug is a cell-permeable molecule that directly inhibits the intracellular kinase of the PDGF receptor as well as the activity of ABL or c-kit kinases. Despite their different structures and mechanisms of action, treatment with hereceptin or gleevec eventually results in kinase inhibition, which shuts down an intracellular communication channel that is critical to the survival of the cancer cell. These drugs therefore demonstrate well the effectiveness of signal transduction therapy of cancer [3] that exploits the dependence of cancer cells on fewer, upregulated signaling pathways. In contrast to healthy cells that can minimize the effect of these drugs by activating alternative signaling networks, cancer cells cannot evade this acute interference in their molecular circuitry, which leads to selective cell death [3].