Understanding how SOX2 can combat BPH

An enlarged prostate is something many men over the age of 60 can look forward to, and the condition, known as Benign Prostate Hyperplasia (BPH), can lead to other more serious health issues. Donald Vander Griend is searching for new creative strategies to cure what is currently an incurable problem.

Donald Vander Griend photo with UI Cancer Center logo
Donald Vander Griend, PhD Twitter: @D_Vander_Griend www.urology-research.com

Vander Griend, PhD, a member of the University of Illinois Cancer Center’s Translational Oncology program and associate professor of pathology at the University of Illinois College of Medicine, has been awarded a five-year $2.5 million grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK, one of the National Institutes of Health) to expand his current research on understanding how the protein SOX2 plays an important role in combatting BPH.

“Prostatic enlargement will only become more prevalent as men’s life expectancy rises,” Vander Griend said. “Today, there is a dire need for alternative therapies to induce and maintain permanent disease remission.”

BPH blocks the flow of urine from the urethra, the duct that transmits water waste from the bladder to the exterior of the body. The prostate cells gradually multiply, creating an enlarged gland that puts pressure on the urethra. As the urethra narrows, the bladder has to contract more forcefully to push urine through the body. The bladder muscle may gradually become stronger, thicker and highly sensitive over time. It begins to contract even when it contains small amounts of urine, causing a need to urinate frequently. Eventually, the bladder muscle cannot overcome the effect of the narrowed urethra so urine remains in the bladder and it is not emptied entirely.

Symptoms of BPH include frequent urination; the sensation that the bladder is full, even after having just gone to the bathroom; the flow of urine is weak, or dribbling occurs at the end; difficulty starting to urinate; having to stop and start several times during urination; and urine leakage, according to the American Urologic Association (AUA).

Current treatment options for an enlarged prostate primarily use therapies targeting the androgen receptor (AR) – proteins in cells which bind the hormones testosterone and androgen, Vander Griend said. Symptoms can be partially alleviated but the disease is not permanently cured. Vander Griend’s laboratory recently discovered that the transcription factor SOX2 is important in the survival of stem and progenitor cells, and can promote stem cell gene expression, repress differentiation, and promote prostate over-growth.

“Our new work will define the mechanism of how SOX2 maintains multi-potent progenitor cells and promotes prostate enlargement,” Vander Griend said. “We believe this new knowledge will be advantageous in exploiting SOX2 and SOX2-target genes as new therapeutic targets to prevent and treat age-related prostate enlargement.”

The long-term goal of the project, Vander Griend said, is to identify signaling pathways regulated by SOX2 in prostate epithelial cells that can be directed to prevent and therapeutically treat prostate enlargement. Defining how SOX2 promotes the survival of multipotent prostate epithelial cells and contributes to expanding prostate stem cells and enlarging the gland will allow the testing of novel strategies to deplete prostate progenitor cell populations.

“We theorize that the number of SOX2-positive prostate cells increases during aging, and SOX2 enables resistance to AR-targeted therapies, thereby promoting prostate enlargement,” he said. “Part of our grant is aimed at trying some drugs that we think will potentially kill these SOX2-positive cells and prevent both BPH and prostate cancer. A major outcome of our work, when it’s concluded, is that we will have identified some novel drugs that we can begin testing in pre-clinical trials.”

Prostate cancer is the most common cancer and second leading cause of cancer death among men in the United States, according to the National Cancer Institute. Prostate cancer accounts for 11% of cancer cases in Illinois, and 9% of cancer cases in the UI Cancer Center’s catchment area. African Americans comprise the majority of cases (64%) in the catchment area, with 18% being non-Hispanic Whites and 17% Hispanic, according to electronic health record data from the UI Health Tumor Registry and UI Health Clinical Data Warehouse.

The age range of prostate cancer cases is 41 to 97 years of age, with the mean age at diagnosis 63. The mean age at diagnosis is three years younger for African Americans (61-years-old) compared to Non-Hispanic Whites (64). Fourteen percent of the cases are stage 1, 44% stage 2, 22% stage 3 and 4% are of an unknown stage. Twenty percent of those diagnosed at stage 1 are non-Hispanic White, compared to only 13% of African Americans.

Translate »