Using complex models of colorectal cancer to understand therapeutic resistance to KRAS/BRAF inhibition.
Owen Sansom
Cancer Research UK Scotland Institute, Glasgow, UK
There is currently huge excitement about the use of KRAS inhibitors for cancer therapy. I will discuss my laboratories experience in generating KRAS and BRAF mutant models of colorectal cancer (CRC) that closely recapitulate human disease. These models have considerable transcriptional heterogenetiy and mimic the different subtypes of CRC. In parallel to clinical observations, KRAS inhibitors do no work as single agents and are associated with rapid resistance and BRAF/EGFR inhibition cause transient response and rapid resistance. I will discuss our latest data on the rapid mechanism of resistance and how we can are investigating new combinations in this space. Finally I will discuss the opportunity for MAPK inhibition to prevent liver recurrence.