Protein Phosphorylation Laboratory, Francis Crick Institute, London, UK.
School of Cancer and Pharmaceutical Sciences, King's College London, Guy's Campus, London, UK.
Nat Rev Cancer. 2021 Jan;21(1):51-63. doi: 10.1038/s41568-020-00310-4. Epub 2020 Nov 11.
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.
癌症基因组中不断成熟的突变全景、临床干预措施的发展和应用，以及对肿瘤相关功能的不断深入了解，揭示了丝氨酸/苏氨酸蛋白激酶蛋白激酶 C（PKC）家族出乎意料的特征。这些进展包括最近的研究表明，与驱动或旁观者角色相关的获得或丧失功能突变，构象约束和可塑性如何影响这类蛋白质，以及新兴的癌症相关特性如何为干预提供机会。肿瘤微环境的深远影响，反映在免疫检查点干预的疗效上，进一步促使人们在这个生态系统中纳入 PKC 家族的作用和干预措施，并深入了解对基质和免疫细胞功能的控制。针对 PKC 同工型的药物治疗有很大的希望，但何时以及如何使用并不明显。
