Clara Bonomi
Research Mentor(s): George WANG
Mentor Department: Pathology-MCTP
Authors: Clara Bonomi, George Wang
Session: Session 6 (3:00pm – 3:50pm)
Presentation Type: Poster 95
Abstract
Prostate cancer is the second most common cause of cancer-related deaths among American men, 36,000 of which are anticipated to die from the disease in 2025. The prostate is located in the male reproductive system and is responsible for producing semen. Common therapeutic approaches to prostate cancer include hormone therapy, chemotherapy, and surgery. However, small molecule protein degraders are promising as a new approach to slow cancer growth. Prostate cancer has been found to be caused mainly by ERG, or “ETS-Related Gene.†The ERG protein is a regulatory transcription factor whose overactivity can cause tumor growth on the prostate. Tomlins et. al first discovered the fusion of Transmembrane Protease Serine 2 (TMPRSS2) and ERG genes as a distinctive characteristic of prostate cancer in 2005. More recent studies have shown that around 50% of prostate cancer cases are caused by ERG overexpression. We have identified several proteins that can bind to ERG and disrupt its translational activity. These ERG inhibitory proteins (EIPs) prevent the ERG protein from binding to its target DNA and slow down cell proliferation. We are working to modify EICs to resemble Proteolysis Targeting Chimeras (PROTAC). These complexes initiate protein degradation via the E3-ubiquitin ligase, an enzyme that will tag ERG protein for degradation via the proteasome. Target degraders like the ones we are developing do not require intensive redosing like hormone therapy, and are not as invasive as surgery or chemotherapy. Thus, our PROTAC-like EIPs present a more approachable solution to slowing prostate tumor growth.
