Artificial signal transduction therapy: a futuristic approach to disease treatment
We highlight the possibility of developing an alternative approach to signal transduction therapy, in which the drugs would be used to generate unnatural cell signaling pathways rather than (or in addition to) affecting the existing ones
A basic property of living systems is the ability to respond to extracellular signals by evoking an intracellular signal cascade, which often leads to changes in gene expression and the resulting phenotypes. In recent years, there has been much interest in developing synthetic molecules that can disrupt the function of signaling proteins and consequently, shut down specific cell signaling pathways. Such molecules have been applied, for example, in ‘signal transduction therapy of cancer’, in which drugs are designed to disrupt malignant, dysregulated pathways.
In this editorial paper we highlight the possibility of developing an alternative approach to signal transduction therapy, in which drugs would be used to generate unnatural cell signaling pathways rather than (or in addition to) affecting the existing ones. These new networks could directly induce, for example, cell death or ‘repair’ or, alternatively, they could be used to activate various different proteins that naturally exist in the cell, but they are not directly involved in the progression of the disease. This idea is supported by our recent study in which a ‘chemical transducer’ enabled a growth factor to activate an unrelated enzyme, which resulted in the selective activation of an anticancer prodrug. In addition, this idea is discussed in the context of other molecular systems, such as chemical inducers of dimerization (CIDs) or synthetic ‘adaptors’ that can connect proteins and induce new functions resulting from these artificial interactions. We hope that this paper will inspire the development of new synthetic agents that can induce artificial signal transduction steps within natural cells, which would bring us closer to achieving ‘artificial signal transduction therapy’.