Abstract

My laboratory has spent a number of years understanding the key consequences of loss of the APC (Adenomatous Polyposis Coli) gene in vivo. Loss of the gene is common to most colorectal cancers (80%) and is thought to initiate CRC . We have found many of our ways to target APC deficient cells stop working when there is additional mutation of KRAS . KRAS is mutated in 40% of CRC and currently acts a negative indicator for EGFR based therapies. In my talk, I will discuss the work we have down investigating the key mechanistic pathways activated in cells that lose both APC and mutate KRAS . I will focus on our work on metabolism and particularly the SLC7A5 (LAT1 transporter) that link metabolism into protein synthesis.

Finally I will discuss our work developing metastatic models of CRC and key determinants of KRAS mutant CRC . Once again these studies have identified a key role for neutrophils in these models.