Scott Dehm, Ph.D., has a message for prostate cancer cells: Resistance is futile.
Dehm, a Masonic Scholar and assistant professor in the Medical School’s Department of Laboratory Medicine and Pathology, is exploring genetic changes that allow prostate cancer to become resistant to hormone treatment.
For men with prostate cancer that persists after surgery or radiation therapy, the next step is to deprive the tumor of androgens—“male” hormones such as testosterone. When androgen receptors inside prostate cancer cells attach to testosterone, the receptors are prompted to move to the cells’ nuclei and activate genes that help the tumor survive and grow. Androgen depletion treatment works by shutting down that signal but only for a while.
In Dehm’s laboratory, researchers are starting to understand ways that prostate cancer cells eventually become resistant to this type of treatment. In response to androgen deprivation, the androgen receptor gene can undergo structural changes that allow the receptor to be active—promoting tumor growth and survival— even without the usual signal from testosterone.
The researchers’ next step is to determine how prevalent these changes are in men with prostate cancer. They also want to know whether genomic information, such as the precise structure of the androgen receptor gene in a patient’s tumor cells, can help predict how individual tumors will respond to different ways of blocking androgen receptor activity.
“This could help oncologists determine if their patient will respond to one [treatment] approach versus another, which is at the heart of personalized therapy,” says Dehm.
He notes that his Masonic Scholar award has been an important source of funding for his work. “For a new investigator, startup funds are absolutely crucial to get projects to the point where we can compete at the national level.”
Ultimately, Dehm and his team hope to develop new treatments for prostate cancer.
“Our work has shown that we may not be able to rely on iterations of the same strategy for blocking the androgen receptor in prostate cancer,” Dehm says. “Therefore, we’re now looking at alternative regions of the androgen receptor protein that could be targeted for the development of new therapies.”