Research Title: “New therapeutic approaches to estrogen receptor-positive breast cancer
Eighty percent of newly diagnosed breast cancer cases are Estrogen
receptor-positive (ER+). More than twenty percent of these patients
are projected to die despite anti-estrogen therapy. Currently a lack
of effective preclinical models of human Estrogen receptor-positive
breast cancer has hampered efforts to find better treatments. Our
goal is to develop better human tumor models to test new drugs and
treatment options. In our work thus far, we revealed DNA repair pathway
deficiencies in our aggressive patient-derived Luminal B tumor models
that could lead to more targeted therapy. Our expectation is that further
study will yield insights that can be rapidly adapted to clinical trials for
patients with Estrogen receptor-positive breast cancer of the aggressive
Luminal B subtype.
Professor, Pharmacology & Toxicology, Medical College of Wisconsin
Research Title: “A novel strategy to suppress the activity of oncogenic small GTPases in breast cancer”
Breast cancer remains a leading killer of women, and our researchis aimed at developing better treatments for breast cancer. We areidentifying new therapeutic targets that promote breast cancer anddeveloping drugs that inhibit their cancer-causing properties. Wediscovered that SmgGDS helps breast cancer cells form tumors byactivating a group of tumor-promoting proteins called small GTPases.
Our goal is to stop breast cancer cells from using SmgGDS to formtumors. We have developed a promising compound called a spliceswitchingoligonucleotide (SSO) that alters the production of SmgGDSin breast cancer cells. We are exploring the use of this SSO compoundas a new strategy to treat breast cancer.
Pharmacology & Toxicology
Research Title: “Stat5 and Anti-Androgen-Induced Metastatic Phenotype of Prostate Cancer”
Treatment options for metastatic prostate cancer (MPC) are
limited to androgen-deprivation-therapy. The new-generation antiandrogen, Enzalutamide dominates the clinical space and is FDA
approved in pre- and post-chemotherapy settings. Resistance to
Enzalutamide arises within 3-6 months, with patients developing terminal
castrate-resistant (CR)-MPC. There are no effective therapies for CR-MPC.
Our data support a novel concept that Stat5 promotes development of
Enzalutamide-resistant prostate cancer (ERPC). We previously showed
that Stat5 induces metastatic behavior of PC cells. Also, Enzalutamide
has been shown to induce metastatic phenotype of PC. Our new data
show that Enzalutamide induces Jak2-Stat5 activation in PC. This proposal
will test whether Enzalutamide induction of Jak2-Stat5 signaling in PC
mediates Enzalutamide promotion of CR-MPC and may result in a new
therapeutic strategy for ERPC by exploiting Jak2-Stat5 pathway inhibitors
that are in clinical development for leukemias. Our goal is that this project
results in development of a new therapy for ERPC.
Each year, our Scientific Review Committee evaluates proposals from researchers at the Medical College of Wisconsin (MCW) to choose the most promising studies that are aligned with the mission of WBCS. We play an active role as a partner of MCW.