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UC Davis Comprehensive Cancer Center

UC Davis Comprehensive Cancer Center

Few but mighty: urologists driving cancer research

Prostate Cancer Program targets androgen independence

UC Davis Cancer Center urologists © 2010 UC RegentsThey are relatively few, but the men and women of the UC Davis urology department have created a research powerhouse. Their cutting-edge work, especially in prostate cancer, is leading the way toward better therapies and outcomes for patients.

A recent analysis of National Institutes of Health funding for schools of medicine found that the UC Davis urology department was ranked third in the nation, with nearly $4 million in research grants in 2008.

Major research commitments bolster UC Davis’ comprehensive clinical approach to prostate cancer, says Christopher Evans, professor and chair of urology.

“Patients not only have the opportunity to get into clinical trials, but we as clinicians have an insight from our molecular research to help us understand what is going on in patients,” he says. “We aren’t just treating the cancer, we are treating the disease process.”

The NIH research data, compiled by the nonprofit Blue Ridge Institute for Medical Research, found that UC Davis has the only urology department in the nation to rank among the top three institutions receiving NIH funding the past three years.

Evans notes that the other top-funded urology departments are much larger than UC Davis’ department, and that of the eight urology faculty members at UC Davis, four have funding for basic science research. “That is unparalleled,” he says. “We have a unique department.”

Evans points to Ralph deVere White, cancer center director, as the architect of UC Davis’ strong urology research team.

urology patient

“Ralph put prostate cancer investigators together with the goal of translational research,” Evans says. “This has facilitated many new projects throughout the UC Davis community.”

The major theme of the UC Davis prostate cancer program is the role of the male hormone androgen and androgen receptors in prostate cancer. In early stages, prostate cancer tumors depend on androgen to grow, so treatment with drugs to counter androgen production have long been used to slow their growth. Unfortunately, when the cancer progresses, this treatment method stops working, and the disease cannot be cured.

UC Davis urology researchers are working to identify the mechanisms that that lead to the development of so-called “androgen-independent prostate cancer.” The hope is that understanding the mechanisms will lead to more effective approaches to advanced disease.

DeVere White and colleagues, for example, identified a specific type of microRNA (strands of RNA that regulate gene expression) that supports the ability of prostate cancer cells to exist and grow, even in an androgen-independent state.

In her laboratory, Paramita Ghosh, an associate adjunct professor in urology and biochemistry, is working on a specific protein called Filamin A, which helps prostate cancer cells metastasize, and prevents cell death even when anti-androgen drugs are used.

“Patients not only have the opportunity to get into clinical trials, but we as clinicians have an insight from our molecular research to help us understand what is going on in patients. We aren’t just treating the cancer, we are treating the disease process.”
— Christopher Evans

Evans and urology department research director Allen Gao have identified the molecular pathways from which other proteins reactivate the androgen receptors, allowing tumors to grow.

Gao’s laboratory also is looking at the role of a cytokine called Interleukin 6 (IL-6) in prostate cancer. “We found that not only does IL-6 activate the androgen receptor,” says Gao, “but it can regulate androgen synthesis inside the prostate, allowing prostate cancer cells to escape anti-androgen therapy.”

Gao says these findings have led to use of a trial combination therapy for prostate cancer that includes anti-androgen drugs with a novel anti-IL-6 drug.

The laboratories of Evans and Hsing-Jien Kung have identified an oncogene called Src kinase, and they are now testing a novel drug developed by Astra Zeneca designed to block it.

“The pill prevents transmission of signals from the cell surface and the activation of the androgen receptor,” says Evans.

Dr. Kung with Randi Kim © 2010 UC Regents

The drug also is being tested in patients with breast and prostate cancer whose diseases have spread to the bones. “We find that the drug not only inhibits cancer cell growth in the bone, but inhibits the bone cells from expressing growth factors that stimulate cancer growth,” Evans says.

A very different, but equally important kind of research is being done by UC Davis urological oncologist Theresa Koppie. Koppie has had a long-standing interest in evaluating disparities in quality of care for urologic cancers.

“It has become clear that patients who are poorer have worse cancer outcomes,” even when you control for clinical factors such as the grade or stage of disease when the patient first accesses care, Koppie says.

With a new, three-year grant from the Department of Defense, Koppie is examining data from hundreds of thousands of cancer patients to study patterns of care and their impact on patient outcomes.

“I think it is multifactorial,” Koppie says. “Genetics play a role to some extent, and you have environment, as well as access to care. But the factor that has not been well-studied is quality of care.”

Koppie hopes her work will ultimately identify things that can be done to address outcomes disparities for people of lower socioeconomic status.

“Down the road, if there are cultural factors at play, we can find interventions to overcome those,” she says. “If there are physician or health-system factors, we can institute quality of care improvements.”