Project 2
"Cellular and molecular responses to targeted therapy"
Principal Investigators: Michael Korn, Frank McCormick
University of California, San Francisco, Comprehensive Cancer Center
Many genetic and epigenetic alterations involved in tumorigenesis and
tumor progression have been identified and efforts are underway to therapeutically
exploit this information. At the same time, it has become clear that affected
cellular pathways regulating cell growth, proliferation, differentiation,
and death are complex, non-linear networks of molecules that can have
redundant functions and are modulated in their activity by cross talk
and feedback mechanisms. The goal of this project is to contribute to
the development of a computational model of signal transduction networks
that predicts cellular responses to pathway targeted therapeutic agents.
We will begin by broadly perturbing signal transduction pathways involved
in cancer progression to generate data for the development of the Pathway
Logic model in Project 1 and we will then focus on validation of model
predictions involving Raf-MEK-ERK signaling and targeted therapeutics
to this pathway.