Claudia Benavente, PhD

Small cell lung cancer (SCLC) is a highly aggressive and metastatic disease that represents the deadliest form of lung cancer. Despite significant effort, there is a lack of precision medicines to treat SCLC patients, who continue to rely on radiation and chemotherapy. Patients diagnosed are in desperate need of improved therapeutic options. We identified a new protein with therapeutic potential called UHRF1 that is critical for SCLC. However, there are no known inhibitors to target UHRF1. UHRF1 is a protein that is naturally tightly controlled by a cellular machinery that functions to eliminate proteins within the cell. This creates an opportunity as drugs that turn off the enzymes that regulate UHRF1 disposal have already been developed. We will exploit this natural protein-eliminating system for the treatment of SCLC. We will determine if these drugs can be used as a therapeutic intervention to stop the proliferation and metastasis of SCLC.

Update:

Our work so far suggests UHRF1 and USP7 are attractive targets for therapeutic intervention in SCLC. Targeting these proteins results in decreased tumor growth in animal models of the disease and prevents dissemination of tumor cells to distant organs. Furthermore, they seem to elicit an anti-tumor immune response. In particular, we found a robust anti-tumor response when targeting USP7, making it a promising target for intervention and a fantastic as inhibitors of USP7 are already available for testing. The assessment of these inhibitors in animal models of SCLC is planned for the second year of this award.