SUMMARY
The research done in the laboratory of John R. Hawse IV, Ph.D., focuses mainly on sex hormone signaling, estrogen receptor biology, and new therapeutic targets in breast and ovarian cancers. The collaborative laboratory has expertise in molecular biology, biochemistry, chemistry, bioinformatics and translational research.
Dr. Hawse's group uses various techniques to address how breast and ovarian cancers respond to specific genes and treatment plans. The lab's areas of study include genome editing using CRISPR, functional omics, genetically engineered models and clinical trials.
Dr. Hawse's research has been well funded for the past 15 years. Organizations supporting his work include the National Institutes of Health, Department of Defense, Breast Cancer Research Foundation, Prospect Creek Foundation, Harold E. Eisenberg Foundation, Susan G. Komen, Minnesota Ovarian Cancer Alliance and Mayo Clinic.
Focus areas
Breast cancer. Dr. Hawse and his group continue to study and develop endoxifen as an alternative therapy to treat newly diagnosed and metastatic estrogen receptor alpha (ERα) positive breast cancer. Previous work in the lab and with others has proved this to be an effective treatment across multiple stages of disease. Current efforts focus on demonstrating targets of endoxifen beyond ERa that may explain why this drug acts so well against cancer. His group has created the first models of endoxifen resistance. As a result, his group has found new treatment targets to improve patient outcomes.
Dr. Hawse's group also has pioneered the study of estrogen receptor beta (ERβ) in breast cancer. His group was the first to prove that this form of the estrogen receptor is found in triple-negative breast cancer. In this type of breast cancer, his group proved that ERβ acts against cancer when activated with estrogen or other substances that enhance ERβ activity. Ongoing work aims to define the molecular mechanisms involved in the tumor-suppressive functions of ERβ. This includes completing a clinical trial to study how effective this approach is in people with highly resistant metastatic breast cancer.
In recent years, CDK4/6 inhibitors have revolutionized outcomes for patients with primary and metastatic breast cancer. But when cancers progress while patients are on CDK4/6 inhibitors, the most cytotoxic treatment options provide only a few months of benefit at best. Dr. Hawse's team is making major efforts to understand the basis for CDK4/6 inhibitor resistance and find alternative ways to treat resistant forms of disease.
Ovarian cancer. Outcomes of an epigenetic drug screen found lestaurtinib to be a highly effective treatment for chemotherapy-sensitive and chemotherapy-resistant forms of high-grade serous and epithelioid ovarian cancer cell lines. Further study of this drug showed that it strongly suppressed JAK-STAT signaling across multiple model systems. Ongoing studies aim to determine how activating JAK-STAT signaling within the tumor microenvironment affects disease progression and sensitivity to standard treatments. The group is studying how disrupting this pathway can help treat patients.
CTPS1 is a gene responsible for converting uridine triphosphate to cytidine triphosphate (CTP). Using publicly available and laboratory-created genome-wide CRISPR studies, Dr. Hawse's team learned that eliminating CTPS1 kills high-grade ovarian cancer cells. With Step Pharma, a startup drug company, the research team is moving a first-in-class and orally bioavailable CTPS1-targeting compound into early-phase clinical trials for this disease.
Significance to patient care
Dr. Hawse's research will continue to help find and create new treatments for various forms of breast and ovarian cancers. These efforts are designed to reduce disease rates related to drug-induced toxicity and lower the death rate of these diseases. His group's work could impact thousands of patients each year.