Monique KaukeDevelopment of novel protein constructs for inhibition of mutant K-Ras function

Approximately thirty percent of all human cancers harbor a mutation in Ras proteins, of which mutant K-Ras is the most commonly implicated in malignancies of the pancreas, colon, and lung. It has been estimated that about 140,000 new cancer cases containing mutated K-Ras arise each year in the United States. Staggering statistics such as these motivate the development of K-Ras targeting drugs, but despite the enormous scientific effort that has been put forth, K-Ras remains undruggable.

Using yeast surface display and a novel protein scaffold, highly stable binders to mutant K-Ras were engineered in our lab. In this project, we seek to develop protein constructs capable of targeting and delivering these binders to cancer cells and evaluating their potential as therapeutic agents.