Final Report Summary - CANCERINNOVATION (Using novel methodologies to target and image cancer invasion and therapeutic resistance)
SUMMARY
This project set out to combine and integrate new technologies in order to decipher the mechanisms of action of key adhesion-linked tyrosine kinases in cancer, and determine how best to use inhibitors against these as effective new therapies. To this end, we co-developed new approaches to discover their modes of regulation, particularly for focal adhesion kinase (FAK), and new cancer cell vulnerabilities involving FAK. We discovered how FAK lies at the heart of protein networks at sites of adhesions, and controls and coordinates cell adhesion and migration with nuclear transcription responses, especially when cells are stressed or transformed into cancerous cells. This has suggested the potential value of combination therapies involving FAK inhibitors, and novel types of drug screens, phenotypic screens, revealed the huge potential value of specific combinations. Crucially, we identified FAK as a regulator of anti-tumour immune evasion, through previously unknown nuclear functions - and this has led directly and rapidly to clinical trials testing a combination of FAK inhibitors and immunotherapies.
This project set out to combine and integrate new technologies in order to decipher the mechanisms of action of key adhesion-linked tyrosine kinases in cancer, and determine how best to use inhibitors against these as effective new therapies. To this end, we co-developed new approaches to discover their modes of regulation, particularly for focal adhesion kinase (FAK), and new cancer cell vulnerabilities involving FAK. We discovered how FAK lies at the heart of protein networks at sites of adhesions, and controls and coordinates cell adhesion and migration with nuclear transcription responses, especially when cells are stressed or transformed into cancerous cells. This has suggested the potential value of combination therapies involving FAK inhibitors, and novel types of drug screens, phenotypic screens, revealed the huge potential value of specific combinations. Crucially, we identified FAK as a regulator of anti-tumour immune evasion, through previously unknown nuclear functions - and this has led directly and rapidly to clinical trials testing a combination of FAK inhibitors and immunotherapies.