Unraveling cancer's secrets
UC Davis Comprehensive Cancer Center's Molecular Oncology Program leads the way
Wolf-Dietrich Heyer might never have extended his research vision much beyond the tiny yeast before UC Davis Comprehensive Cancer Center recruited Hsing-Jien Kung as an associate director to beef up the basic research effort.
Kung has since retired, and Heyer’s work is now the backbone of one of UC Davis Comprehensive Cancer Center’s six research programs, the Molecular Oncology Program, which includes a growing cadre of scientific stars working to unravel cancer’s molecular secrets to better diagnose and treat the disease.
Heyer’s work could apply in 70 percent of cancer patients, whose cancer involves malignant cells that are resistant to treatment. His work aims to find ways of making cancer cells more susceptible to anti-cancer treatments by understanding and manipulating the mechanisms that make cancer cells hard to kill.
Heyer and his team focus on repair of DNA breaks. It turns out DNA breaks all the time, which should be fatal to the cell. But cells can repair their broken DNA, even when both strands of the double-stranded DNA break.
This process likely relates to cancer, Heyer says. Chemotherapy and radiation treatment are intended to damage DNA, leading to cell death. But some cancer cells are not susceptible, suggesting that one mechanism might be a better-than-average ability to repair their damage.
The future: personalizing cancer treatment
The focus in Heyer’s laboratory has been on “RAD” proteins, a term short for “radiation sensitive.” The group was so named because genetic defects, or mutations, in RAD proteins sensitize cells to radiation and other DNA damage induced by chemotherapeutics, impairing DNA repair. Hundreds of proteins are involved in DNA repair, but the key questions Heyer wants to answer are: Which are the central proteins for repair of DNA damage induced by cancer therapy and what are they doing, exactly?
“UC Davis has been able to recruit top young talent in basic cancer research, and they have had spectacular success.”
— Wolf-Dietrich Heyer
The research could result in ways to interfere with the repair process and make tumor cells more susceptible to radiation and other cancer treatments. Heyer says it may lead to a day when new cancer patients come to the clinic, are tested for their RAD-gene profile and ability to repair DNA, then have their treatment tailored to their cancer’s ability to repair itself and withstand the treatment.
“This will lead to personalized medicine,” he says. “Our effort is to establish the basic science and help translate these insights into the clinic.”
Paul Henderson, an assistant professor in the program, already is exposing cancer cells to platinum, the toxic substance in a few chemotherapy drugs, to see if such a test could be a marker of a person’s potential treatment response.
Another program investigator, Stephen Kowalczykowski, a professor of microbiology and molecular genetics, has developed a way to tag the molecules involved in DNA repair with a fluorescent probe, with which he can actually watch the repair process as it occurs. And Neil Hunter, a rising star sponsored by the leading biomedical sciences philanthropy, the Howard Hughes Medical Institute, has developed strategies to analyze complex DNA structures that occur as cells repair DNA damage.
Heyer says the Molecular Oncology Program has a number of inspired scientists such as Kowalczykowski and microbiology professor John Roth, who are members of the National Academy of Sciences, a very exclusive fraternity.
Other key areas of molecular oncology research
Another key area of research in the Molecular Oncology program is how cancer cells process signals that control growth. “This is at the very heart of cancer,” says Heyer, “because cancer is a disease caused by cells that can’t stop multiplying.”
Professor of biochemistry and molecular medicine, Hongwu Chen, focuses on signaling, in particular the effect of hormone signaling in breast and prostate cancer. This thrust is amplified by Martin Privalsky, another member of the program and a renowned leader in understanding how hormones regulate the activity of genes.
Elva Diaz, assistant professor of pharmacology, was awarded an NIH Director’s Innovation Award for her work on the development and growth of neurons in the brain as a window into understanding brain tumors, a particularly devastating form of cancer. She focuses on a type of brain tumor most common in children known as medulloblastoma.
Add to this line-up Kate Rauen, director of the newly established UC Davis Advanced Translational Genomics Center (ATGC), an expert on RAS signaling, a pathway associated with many cancer types and other human diseases. Rauen directs a comprehensive research program that spans basic research all the way to the clinic, and is also teaming up with molecular oncology member John Albeck, who developed methods to visualize the activity of the RAS signaling pathway in real time in live cells.
All this fire power in signaling has propelled the basic science to the clinic, a particularly satisfying development for such a young program as ours, according to Heyer.
Looking at the new generation of cancer researchers in the program, Heyer is especially optimistic about the future: “UC Davis has been able to recruit top young talent in basic cancer research, and they have had spectacular success.”