Dr. Lily Wu: Unlocking the Secrets of Metastatic Cancer

Lily Wu grew up in a house of engineers. While her science is just as exacting, Wu took a different path—cancer research.

“I was always quite keen on biology in animals and in people, so I thought I would become either a biologist or a doctor,” said Wu, who did both.

She earned her doctorate and medical degrees concurrently in six years through a UCLA program designed to increase the numbers of physician-scientists. She’s quick to point out that what she does is not so dissimilar from what the engineers in her family are doing.

“The engineers are always working on ways to improve upon things,” said Wu, who is an associate professor of urology. “I spend my time thinking about how to improve cancer care and make things better for patients. My dad and I always joke that he builds and fixes cars and I fix people.”

Born in China, Wu and her family escaped the cultural revolution by fleeing to Hong Kong in 1967 when she was 7-years-old. They lived in Hong Kong for nearly a decade, moving to the United States in 1975, when Wu turned 16-years-old.

They settled in Davis, California, where Wu attended high school. She graduated in 1983 from the University of California, Berkeley, then studied at the University of California, San Francisco for a year before joining the M.D./Ph.D. program at UCLA.

After earning her degrees and completing her residency, she received a prestigious four-year Howard Hughes Medical Institute fellowship to hone her research skills. She joined the UCLA faculty in 1998. Now an associate professor of urology and pharmacology, Wu’s research is aimed at developing a better understanding of cancer biology and improving gene-based therapy.

Specifically, Wu is re-engineering a microscopic common cold virus so it can deliver a genetic payload to cancer cells. The payload, in turn, performs a range of tasks to help manage the cancer. Using positron emission tomography (PET), the clinician can image tiny prostate cancer metastases that can’t be seen using traditional imaging tools. It also can be made toxic to destroy the cancer cells.

Currently, physicians don’t know if a treatment is attacking the cancer cells until they use traditional imaging methods such as CT scanning to show a decrease in tumor size. That can take months. And if the treatment isn’t working, the patient is subjected to a toxic therapy that is not helping.

Wu believes linking the imaging and treatment steps is the most powerful aspect of her work. One day she will be able to locate these tiny metastases in humans and kill them at the same time, while watching it all on a PET scanner.

“I’m a person for whom seeing is believing,” Wu said. “And that is what imaging allows me to do. I can visualize the entire treatment process—the engineered virus getting to the cancer, treating it and making it go away. If what you’re doing is working, you’ll see it right away. If it’s not working, you can change course.”

In Wu’s initial studies in mice, she used the engineered virus to deliver a specially-designed gene called “sr39tk,” which has dual functions, to produce PET signals and provide a dormant killing function that can be activated later. Wu was able to show that the sr39tk was successfully produced in the prostate tumor and emitted a strong PET signal. Then, she gave a drug to the same animal that activated the killing function and watched the PET signal disappear, meaning the disease was gone. Now she’s working to refine the process, make it more efficient and reproduce the same results in patients.

Her work was initiated with the support of a interdisciplinary grant from UCLA’s Jonsson Comprehensive Cancer Center. Since then, Wu co-developed TSTA, a two-step transcriptional amplification method that increased the expression of the genetic payload inside the cancer cell—in effect boosting the imaging signals and killing activity of the engineered virus.

Recently, Wu was able to show that the targeted strategy she developed works for treating lymph node metastases. Her research suggests that lymph nodes are where the cancer first goes when it spreads, before it moves to other vital organs. The critical next stage of her research is to image and kill the cancer cells at the lymph nodes, preventing spread to other organs, the metastatic stage of the disease that is often fatal.

She hopes to translate this work into human subjects within the next two years.

“It’s very gratifying to see our work move from the concept stage to validation stage in animals,” Wu said. “I’m excited that translating our work to people is in sight.”

By Kim Irwin, 2007