Kinase Drug Discovery: Modern Approaches
CHAPTER 12: Kinase Inhibition for Immuno-oncology
Published:31 Oct 2018
Special Collection: 2018 ebook collectionSeries: Drug Discovery
K. J. Duffy and C. A. Parrish, in Kinase Drug Discovery: Modern Approaches, ed. R. A. Ward and F. W. Goldberg, The Royal Society of Chemistry, 2018, pp. 313-358.
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A new era of immunotherapeutic intervention in oncology was ushered in by the approval of ipilimumab in 2011, a CTLA4 blocking antibody for the treatment of melanoma. The ensuing approval of several PD-(L)1 immune checkpoint-blockading agents demonstrated that durable responses could be realized in a disease where only a modest delay to progression was the standard outcome. All these therapeutic antibodies act through modulating the inter-cellular communication network employed by the immune system. However, such modalities are unsuited to attenuate intra-cellular signaling pathways, which currently remain the domain of small molecule therapeutics. Discussed herein are kinase targets and small molecule inhibitors thereof that have found utility in immuno-oncology. An emphasis in this review is placed on molecules and targets under clinical evaluation, although emerging areas of exciting preclinical biology will also be discussed.