Grant: Fellowship: Bisby (Prize)

In the western world, cancer accounts for one in three deaths as well as causing significant social and economic impact. This Fellowship proposal seeks to decipher how drugs that act to inhibit protein synthesis can kill cancer cells. Recently, there has been much interest in this class of drugs especially for treating cancers of the blood. One, homoharringtonine has successfully undergone clinical trials and another, silvestrol, proved to be efficacious in mouse models of multiple cancer types. I plan to investigate whether these drugs trigger cell death by causing apoptosis, an evolutionarily mechanism of cell suicide that is deployed to remove damaged or unwanted cells. Pertinently, this pathway is often defective in cancer cells which accounts for the persistence of tumor cells. I shall also explore if the combination of drugs that act to inhibit protein synthesis with those directly activating cell suicide could be effective in mouse cancer models. These studies will provide a greater understanding how these anti-cancer agents act and will critically presage how they can be tested and used in the clinic for treating patients with cancer.