Going the Distance Together

reprinted from Issue 21, Fall 2015 of Frontiers of Medicine (PDF)

Division Highlight: The Genitourinary Medical Oncology Program

Charles Ryan, MD, Thomas Perkins Distinguished Professor in Cancer Research, leads the UCSF Genitourinary Medical Oncology Program.

"Research and being a good clinician are tightly interwoven,"said Charles Ryan, MD, Thomas Perkins Distinguished Professor in Cancer Research, who leads the UCSF Genitourinary Medical Oncology Program. He and his team care for patients with prostate, bladder, kidney and testicular cancers. Many of the program's investigations focus on prostate cancer, which affects about one in seven American men.

"Prostate cancer is among the most heterogeneous cancers,"said Ryan. About one-third of patients don't need treatment, one-third are cured with treatment, and one-third die despite all treatment. "Our goal is to not over-treat patients who don't need it, provide effective therapy to those who can be cured, and develop new therapies for those who currently die of the disease," he said.

Prostate cancer is driven by testosterone. Hormone therapy is one of the most effective treatments; by depriving men of testosterone, it helps keep prostate cancer in check. However, the cancer can become hypersensitive to low levels of testosterone and recur. "It's like a hybrid car,"said Ryan. "When the price of gasoline goes up, people stop driving gas-guzzlers, and cars evolve to become more fuel-efficient. That's similar to what happens with prostate cancer, which evolves to use less testosterone. Sometimes, the disease evolves into an electric car – something so completely different that we can't target it with existing therapies.”

"We are at such a turning point in the field,"said Eric J. Small, MD, chief of the Division of Hematology and Oncology at UCSF Medical Center and deputy director of the UCSF Helen Diller Family Comprehensive Cancer Center. "In the 25 years that I've been doing this, I've never been more excited. UCSF is advancing the standard of care, not just learning about it at conferences.”

The Genitourinary Medical Oncology Program has pioneered many novel treatments, including:

Development of new drugs:

The team, including Small, Ryan and Lawrence Fong, MD, developed and obtained FDA approval of two new prostate cancer drugs: abiraterone acetate (Zytiga), which helps patients whose cancer has progressed despite standard hormone therapy, and sipuleucel-T (Provenge), which harnesses the body's own immune cells to fight cancer. They are also testing another immunologic drug, ipilimumab (Yervoy), which has been approved for melanoma and has shown promise in prostate cancer. Pamela Munster, MD, and Rahul Aggarwal, MD, spearhead efforts to develop early phase clinical trials of new therapeutics.

Precision medicine:

With $10 million in support from Stand Up To Cancer and the Prostate Cancer Foundation, Small leads a multi- institutional "Dream Team"in genetically sequencing tissue samples from 300 patients with metastatic prostate cancer. By identifying different subgroups of prostate cancer, they are learning why some people develop resistance to therapy, and hope to customize treatments that target vulnerabilities of an individual's particular cancer.

Developing less invasive surveillance tools:

In partnership with the Department of Radiology and Biomedical Imaging, the program is developing a novel imaging technique to monitor the aggressiveness of prostate cancer without biopsy. Similarly, UCSF is developing "liquid biopsies,"in which prostate cancer could be monitored by analyzing blood samples.

Comprehensive care:

Aggarwal leads the Supportive Therapy in Androgen Deprivation (STAND) Clinic, which educates patients about exercise, nutrition and the effects of hormone therapy on quality of life and how to manage side effects of treatment. "Patients experience profound changes when we take away testosterone, and we have a tremendous amount to learn about the biological, oncological and psychological effects,"said Aggarwal.

The UCSF Genitourinary Medical Oncology Program, in collaboration with the Movember Foundation, is also launching an international clinical trial to study whether increased exercise can improve life expectancy. "There is a strong interface between the endocrine system and prostate cancer,"said Ryan. "We've known about the effect of testosterone on prostate cancer for decades, but there is also a relationship between sugar metabolism and cancer progression, and perhaps even cholesterol metabolism and cancer. Even if exercise doesn't lead to an improvement in cancer outcomes, we might find that it lowers the risk of diabetes, which is a known consequence of hormonal therapy.

"We are trying to address genitourinary cancers in a really broad fashion,"said Ryan, who enjoys collaborating across disciplines and enthusiastically mentors young investigators. "By bringing other people into the field, we can go so much further. There is an African proverb I like: ‘If you want to go fast, go alone. If you want to go far, go together.'"

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