期刊
NATURE REVIEWS CANCER
卷 21, 期 1, 页码 51-63出版社
NATURE PORTFOLIO
DOI: 10.1038/s41568-020-00310-4
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- Francis Crick Institute - Cancer Research UK [FC001130]
- UK Medical Research Council [FC001130]
- Wellcome Trust [FC001130]
- National Institute for Health Research, the University College London Hospitals Biomedical Research Centre
The evolving mutational landscape of cancer genomes highlights unexpected features of the PKC family of serine/threonine protein kinases, providing new insights into potential interventions for tumor development. Understanding the functional properties of PKC isoforms in cancer may offer new opportunities for therapeutic exploitation.
The maturing mutational landscape of cancer genomes, the development and application of clinical interventions and evolving insights into tumour-associated functions reveal unexpected features of the protein kinase C (PKC) family of serine/threonine protein kinases. These advances include recent work showing gain or loss-of-function mutations relating to driver or bystander roles, how conformational constraints and plasticity impact this class of proteins and how emergent cancer-associated properties may offer opportunities for intervention. The profound impact of the tumour microenvironment, reflected in the efficacy of immune checkpoint interventions, further prompts to incorporate PKC family actions and interventions in this ecosystem, informed by insights into the control of stromal and immune cell functions. Drugging PKC isoforms has offered much promise, but when and how is not obvious. This Review discusses protein kinase C (PKC) isoforms in cancer, in particular focusing on their functional properties in the context of tumour suppression or promotion, target validation, PKC pharmacology and therapeutic exploitation.
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