Proteomics‐based interrogation of the kinome and its implications for precision oncology

AbstractThe identification of specific protein kinases as oncogenic drivers in a variety of cancer types, coupled with the clinical success of particular kinase‐directed targeted therapies, has cemented the human kinome as an attractive source of “actionable” targets for cancer therapy. However, “mining” of the human kinome for precision oncology applications has yet to yield its full potential. This reflects a variety of issues, including oncogenic kinase dysregulation at levels not detectable by genomic sequencing and the uncharacterized nature of a considerable fraction of the kinome. In addition, selective therapeutic targeting of specific kinases requires efficient mapping of total kinome space impacted by candidate small molecule drugs. Fortunately, recent developments in proteomics techniques, particularly in mass spectrometry‐based phosphoproteomics and kinomics, provide the necessary technology platforms to address these impediments. Moreover, initiatives such as the Clinical Proteomic Tumour Analysis Consortium have enabled the generation, deposition and integration of genomic, transcriptomic and (phospho)proteomic data for many cancer types, providing unprecedented insights into oncogenic kinases and cancer cell signalling generally. These multi‐omic data are identifying novel therapeutic targets, highlighting opportunities for drug re‐purposing, and helping assign optimal therapies to specific tumour subtypes, heralding a new era of “enhanced” precision oncology.