CHAPTER 14: The Future of Kinase Therapeutics

Many small molecule and protein-based kinase drugs have brought significant benefits to patients worldwide especially in the oncology therapeutic area. Three specific areas that are likely to experience significant growth in the coming decade are highlighted in this chapter. First, activation of protein kinases provides an as yet untapped avenue for harnessing the therapeutic potential of this gene family. Recent progress made in identification of activators of AMP-activated protein kinase demonstrates some of the potential as well as challenges in discovering and developing enzyme activators. Secondly, a new modality that has been gaining some traction recently is the so-called “protein degradation” technology that co-opts endogenous ubiquitin proteosomal machinery to eliminate proteins that are of therapeutic interest. While considerable challenges lie ahead in translating this concept into orally bioavailable drugs, the technology presents unique opportunities for targeting scaffolding proteins, pseudokinases and undruggable proteins. Finally, the oncology arena is poised for even more breakthrough medicines through incorporation of emerging knowledge of drug resistance mechanisms and technological advances in drug design into the discovery process. Real-time characterization of the patient's disease biology and its response to therapy are likely to herald a bright future of keeping cancer at bay by attacking it with patient-specific therapeutic regimens.