Much of the colon cancer research conducted at Huntsman Cancer Institute (HCI) began with one question: What does the adenomatous polyposis coli (APC) gene do? This attempt to understand colon cancer at a genetic level has grown into groundbreaking discoveries that are leading to better treatment and prevention of colon cancer.
David Jones, PhD, Senior Director of Early Translational Research at HCI and a professor in the Department of Oncological Sciences at the University of Utah, came to HCI because of his expertise in pharmacology and his desire to develop drugs that target the genetic causes of cancer. Researchers knew that the APC gene had been linked to causing colon cancer, both in people with genetic risk and in the general population. They needed to know what the gene does in order to develop drugs to correct the defects that result when the gene mutates. “My whole research program for the last 15 years has been trying to understand what this gene does when it’s working normally so we can understand why things go wrong when it’s mutated,” says Jones.
To understand the APC gene better, imagine that each part of your body has a different recipe. When cells start forming in the colon, for instance, they have to follow the colon recipe to turn into a functioning colon cell. The APC gene helps cells read colon recipe instructions. But when the APC gene mutates, the cells that are supposed to become colon cells can’t read the recipe properly and they become irregular cells. This is the beginning of colon cancer, says Jones.
The discovery of the APC gene’s “recipe reading” function is a breakthrough in colon cancer research. “We discovered a whole new function of this gene,” says Jones. “So many people thought the gene had a critical role in causing cells of the intestine to grow out of control. But we think that gene controls the fate of cells—it doesn’t control their growth.”
Because of this discovery and other promising research, the National Cancer Institute (NCI) has awarded HCI a $12.2 million grant to continue colon cancer research. The grant is a renewal of a grant awarded in 2003.
Jones and Randall Burt, MD, a member of the original research team that discovered the APC gene and now HCI Senior Director of Prevention and Outreach, will lead a research team that includes Nobel Prize Laureate Mario Capecchi, PhD; Melinda Angus-Hill, PhD; Diana Stafforini, PhD; and Matthew Topham, MD. The team will focus on both basic science and clinical research.
Says Burt, “The research on this project focuses on the mechanisms involved in causing a cell to form a precancerous polyp, and then cancer. We will also be doing a clinical trial based on findings from the last round of the study. Two medications that perturb cellular mechanisms that lead to cancer will be given to people who have a genetic predisposition to develop precancerous polyps. We expect that polyps will regress and new ones will not form.”
A collaboration between Jones and Brad Cairns, PhD, Senior Director of Basic Science at HCI, parallels the NCI grant work and has yielded some important breakthroughs in colon cancer research. Jones’ interest in cell fating and studying the “recipes” that determine what a cell is going to be led to his work with Cairns. “Cell fating is almost certainly dictated by how your DNA is packaged and interpreted, and how your cells decide what genes to use and what genes not to use,” says Jones. Cairns’ work focuses on chromatin, which packages DNA in the cell's nucleus.
In 2010, the two researchers co-authored a study published in the journalCell that described how an enzyme system is linked to mutations in the APC gene. The study has interesting implications, says Jones. “If we know that people have APC mutations and we know this enzyme is now doing things without the proper control, putting those patients on a drug that affects this enzyme could prevent them from getting cancer in the first place.”
Such collaboration is an example of how HCI researchers leverage the expertise of their fellow researchers in order to achieve a common goal: finding better ways to prevent, detect, and treat cancer.
|Dov Sporin and his children, Sienna and Matan|
Even when Dov Siporin is “off duty” (meaning he is not receiving chemotherapy), he drops by the Huntsman Cancer Institute (HCI) Infusion Center to visit patients, bringing candy (“It tastes better than chemo!”) taking special care to chat with patients who are sometimes uncertain or fearful. For Valentine’s Day, he even dressed as cupid—diaper, wings, and all. “The energy in the room changes when Dov is here,” says Shelley Stoker, clinical care specialist for gastrointestinal cancer patients at HCI. “Everyone just lights up when he comes around.”
Since his diagnosis of stage IV colorectal cancer in January 2008, Dov has become known for his impromptu stand-up comedy routine, playful pranks with staff, and founding Team Tumor, a group of cancer survivors who participate in events that raise awareness and funds for cancer research.
“I started Team Tumor to get others in treatment up and running,” Dov said. “But it’s helped me stay focused on what we can do and not what we can’t.” Dov has completed multiple races, including the Wasatch Back, Top of Utah, and various 5Ks with and without his chemotherapy IV pole.
In the face of adversity with a cancer diagnosis that seems insurmountable, Dov continues to fight. He has completed 3,000 hours of chemo, three months of radiation, and about 25 hours of surgery. Every step of the way, he has made those who meet him feel comfortable enough to laugh in the face of what has been called a terminal cancer. He reminds us that life is urgent—and never, ever boring.