The Wolf Lab
Committed to the study of stress response pathways in cancer and to the development of new prostate cancer therapeutics.
Prostate cancer is the most common male malignancy in the Western World and the second most common cause of cancer-related death in men. Standard care for advanced prostate cancer is androgen deprivation therapy (ADT). While most patients initially respond to ADT, virtually all - about 75,000 per year - develop incurable castration resistant prostate cancer (CRPC). On the basis that CRPC continues to depend on androgen receptor (AR) function, the AR pathway remains the Achilles’ heel of CRPC. Since existing small molecules AR blockers, while effective initially, are rapidly rendered inactive due to AR point mutations, new modalities of interfering with AR function are urgently needed. We are seeking novel targets and small molecule compounds to combat CRPC.
Stress Response Pathways
Many of the targets we are pursuing are components of stress response pathways. Cancer cells are typically subjected to stressful conditions in their tumor microenvironment, and yet escape stress-induced cell death mechanisms. We study how normal cells respond to stress and how stress response pathways are altered in cancer cells to enable their survival. We are also exploring ways of exploiting the stress phenotype of cancer cells and associated vulnerabilities for synthetically lethal drug targeting. The basic framework of these studies is built on understanding molecular mechanisms of protein homeostasis and quality control, principally pathways regulating protein synthesis and protein degradation through the ubiquitin-proteasome system. In these studies, we are frequently employing systems biology approaches such as network analysis and modeling.