Models of molecular diversity in breast cancer to guide marker guided therapy
Joe Gray
UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, USA
Comprehensive analyses of the breast cancer genomes, transcriptomes and proteomes have demonstrated remarkable heterogeneity as well as a significant number of recurrent aberrations that are likely to influence response to approved and experimental therapeutic agents. The challenge is to understand how these aberrations actually do influence treatment, to identify therapeutic agents that will be most effective against molecularly distinct breast cancer subsets and to define molecular markers that predict individual responses. Our approach is based on the use of a collection of 50 breast cancer cell lines as a tractable, in vitro model of breast cancer subtypes and heterogeneity therein. This talk will (a) Review our current understanding of the omic features of the cell lines and the extent to which these features mirror those in primary tumors, (b) Summarize analyses of the biological responses of the cell lines to approximately 40 approved and experimental therapeutic agents that identify molecular correlates of response, (c) Explore integrative analytical approaches to identify pathways that are involved in responses or resistance that may suggest strategies to combine drugs.
