CHAPTER 11: The Importance of Kinase Mutations in Cancer Drug Discovery

Amino acid mutations within a kinase sequence may play a pivotal role on the behaviour of these proteins in various disease settings. These mutations in some cases can activate a kinase, commonly referred to as driver mutations and have become targets of drug discovery projects resulting in numerous approved therapies. In other cases, kinase mutations have been observed as a resistance mechanism to cancer treatments, in some cases such mutations have themselves become the target of future targeted drug discovery efforts leading to multiple generations of therapy. This chapter summarises the broad role of kinase mutations in drug discovery and reflects on the unique opportunities and challenges in the field. To highlight this fascinating area, specific examples including EGFR, ABL, RET, ALK, BRAF, cKIT and TRK are reported as case studies.