News item posted on 2014-03-14

CSB Research Spotlight - Stephen Fesik

Because of its role in cell growth and survival, aberrant Ras signaling can contribute to carcinogenesis. Mutations in RAS genes are among the most common in malignant tumors, present in up to 30% of human cancers. Consequently, inhibitors of excessive Ras signaling are of great interest as potential cancer chemotherapeutic agents. However, attempts to discover small molecules that bind to Ras proteins and interfere with their function have been met with limited success due to the lack of binding pockets on the protein.

Now, Center for Structural Biology and Vanderbilt Institute of Chemical Biology investigator Stephen Fesik and his laboratory have taken a new approach to target Ras by discovering a small molecule that binds to a complex between Ras and the GEF SOS (son-of-sevenless homolog). The results of this study lay the foundation for further study of a new kind of Ras activity modulator that binds to Ras-protein complexes.

View the entire article in the VUMC Reporter. Read Dr. Fesik's paper, "Approach for targeting Ras with small molecules that activate SOS-mediated nucleotide exchange," in the Proc. Natl. Acad. Sci. U.S.A.

Author: Stephen M. Doster