2007

Clodagh O’Shea PhD

The Salk Institute for Biological Studies, CA Associate Professor, Molecular and Cell Biology

Research Focus: Next Generation Oncolytic Adenovirus for Lung and Breast

Cancer Type: Breast Cancer

Award: Young Investigator

Most commonly used chemotherapies are little more than DNA poisons that slow down tumor growth but do not ultimately cure patients. Chemotherapy also has devastating side effects, which are especially tragic in children. There is a desperate need to identify new drugs and therapeutic modalities that ablate cancer cells while leaving normal cells unharmed. The p53 tumor suppressor pathway is inactivated by mutations or gene deletions in almost every form of human cancer. Despite this, there are no effective therapies to treat p53-defective tumors. It is a major challenge to develop small molecule therapies to a cellular target that is either lost or inactivated. We are developing new potent sub-group C and B oncolytic adenoviruses that depend specifically on the loss of p53 functions to drive their tumor selective replication. Each time a virus infects a p53 mutant cancer cell and successfully multiplies, the virus ultimately kills the cancer cell by bursting it open to release thousands of viral progenies, which are ready to seek out remaining tumor cells and distant micro-metastases. These next generation p53-tumor selective replicating viruses have the potential to help save the lives of many cancer patients.

“To develop these viral cancer therapies we will exploit the striking similarities that exist between adenoviral infected cells and tumor cells. Both subvert many of the same cellular checkpoints, including p53, with one difference: in tumor cells, the key cellular players are targeted via mutations, while adenoviruses use viral proteins to achieve the same end.”

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