USC project seeks to answer important questions about cancer

Three groups of University of Southern California (USC) researchers-representing medicine, chemistry and chemical engineering-are recipients of highly competitive grants from the National Institutes of Health's National Cancer Institute (NCI). They seek to answer what the NCI considers to be "important but not obvious questions" about cancer, challenging investigators to study the disease in especially effective and imaginative ways.

Some $22 million is being distributed among the first 56 recipients nationwide to be awarded grants through the NCI's Provocative Questions Project. USC received more awards than any other Southern California institution. Two of the university's three awards went to researchers in the Keck School of Medicine of USC, while the third went to researchers from the USC Viterbi School of Engineering and the USC Dornsife College of Letters, Arts and Sciences.

For a study to be titled "Epigenetic Drivers of Cancer," Peter Laird, director of the USC Epigenome Center and professor of surgery, biochemistry, and molecular biology at the Keck School, submitted a query that led to an award of more than $2.38 million over four years.

"In contrast to the traditional focus on mutations in the DNA, this grant will enable us to pursue an understanding of the less-often studied epigenetic changes in gene activity-changes in how the cell interprets the DNA," Laird said. "My question is: Can we distinguish between 'driver' and 'passenger' epigenetic events that lead to cancer? If we're able to do that, then we can identify which genes actually help to cause the cancer and develop drugs that attack that defect in the cell."

Joining him as principal investigators of the study are Peter Jones, the Sawyer Chair in Cancer Research and a distinguished professor of urology and biochemistry and molecular biology at the Keck School, and Stephen Baylin, deputy director of The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins.

Laird noted that his co-investigators are two of the pioneers in the field of the epigenetics of cancer. In addition, for 17 years, Jones was director of the USC Norris Comprehensive Cancer Center, one of the world's premier institutions for the study of epigenetics.

Darryl Shibata, professor of pathology in the Keck School received more than $220,000 to study "How do NSAIDS [nonsteroidal anti-inflammatory drugs] Prevent Colorectal Cancer?"

Shibata said that several epidemiological studies have shown that in people who take low-dose aspirin for heart health for at least five years, their risk of colon cancer goes down by 10 to 20 percent.

"But no one knows why," Shibata said. "I'm going to test aspirin and another NSAID, sulindac, which is sometimes used as a pain reliever, to try to find out how NSAIDs reduce cancer risks."

Shibata is interested in the stem cells from which cancer develops. "The theory, which I will explore, is that aspirin might reduce the number of stem cells we have in our bodies," he said. "It's only recently that we've been able to count the number of stem cells in mice. It turns out that the colon has many stem cells in it. So, if we could reduce the number with some low-dose aspirin, then might be able to reduce the risk of colon cancer."

The third USC project funded by the NCI seeks to answer the question: "Are there new technologies to inhibit traditionally 'undruggable' target molecules, such as transcription factors, that are required for the oncogenic phenotype?"

In this study, three principal investigators were awarded more than $472,000 to explore whether tumor cells that express certain proteins, and do not respond to standard drugs currently used to fight cancer, can be stopped or prevented with new types of drugs that would block the actions of those proteins.