Equivocal, explicit and emergent actions of PKC isoforms in cancer.
Peter J ParkerSophie J BrownVeronique CallejaProbir ChakravartyMathias CobbautMark LinchJacqueline J T MarshallSilvia MartiniNeil Q McDonaldTanya N SolimanLisa WatsonPublished in: Nature reviews. Cancer (2020)
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.
Keyphrases
- protein kinase
- papillary thyroid
- physical activity
- squamous cell
- randomized controlled trial
- stem cells
- single cell
- bone marrow
- molecular dynamics
- climate change
- intellectual disability
- machine learning
- childhood cancer
- molecular dynamics simulations
- dna methylation
- squamous cell carcinoma
- autism spectrum disorder
- risk assessment
- deep learning
- small molecule