Center News

UCCC turns 20

The University of Colorado Cancer Center turned 20 in February. UCCC was established in 1988. In 1997, it received its comprehensive cancer center designation from the National Cancer Institute in recognition of its full breadth of cancer care, research, prevention and control and education work. Today, UCCC has 405 members from nine member institutions, enrolls more than 6,000 patients in clinical trials, and receives about $110 million in funding.

You can read about many of the things that have happened at UCCC over the past 20 years in Possibilities, our 20th Anniversary Report.

TACTIC Clinic launches July 1

Adult survivors of pediatric cancers now have an innovative clinic to help them transition from pediatric oncologists to internists. The Thriving After Cancer Treatment is Complete, or TACTIC, clinic brings together pediatric oncologists, internists and cancer counselors to provide comprehensive health evaluations that improve survivorship-based care and prevent chronic health conditions.

The clinic is offered the first Thursday of each month. More information: 720-777-0956 or www.uch.edu/tactic.

Progesterone or synthetic progestins can reactivate cancer stem cells

Progesterone or synthetic progestins can reactivate stem cells in small, young breast cancer tumors, UCCC researchers report in the April 7 issue of the Proceedings of the National Academy of Sciences.

Kate Horwitz, PhD, Wendy Dye, MD, Peter Kabos, MD, Chuck Harrell, PhD, and Carol Sartorius, PhD, report that breast cancer progenitor cells lack hormone receptors. Therefore, these stem-like cells may survive hormone therapy and trigger re-growth of new hormone treatment resistant tumors.

Also, they said it is possible that women taking estrogen plus progestin hormone replacement therapy may be at higher risk for breast cancer than women taking only estrogens because the combination therapy reactivates small, undiagnosed, possibly dormant breast cancers.

UCCC members collaborate to reveal Six1 gene’s role in cancer development, metastasis

University of Colorado Cancer Center researchers are collaborating to understand why a gene called Six1 makes some cancer tumors more aggressive, harder to kill and more likely to recur.
 
Andrew Thorburn, PhD, a pharmacologist and UCCC Associate Director for Basic Research, Heide Ford, PhD, a reproductive scientist, Kian Behbakht, MD, a GYN oncology surgeon, and Christine Wu, PhD, a mass spectrometrist, don’t know that solving the Six1 problem will be the silver bullet for stopping aggressive cancers, but they know it will be critical on the path toward personalized medicine.
 
“If we know what genes are over expressed in a tumor, we can target treatment for that specific genetic expression,” said Ford. “We’ve seen that with HER+ breast cancer and Herceptin and estrogen receptor-positive cancer and Tamoxifen. We believe we will be able to do the same for Six1-positive tumors.”
 
Six1 is critical in normal embryo development, causing cells to make specific kinds of tissues and  organs, and to migrate to the correct location in the body—all of which are stem-cell-like properties. Eventually, the gene is turned off.
 
Ford discovered that Six1 is over expressed—turned on and in higher than normal quantity—in 50 percent of primary breast cancers and 90 percent of metastatic lesions. Through examining publicly available data, she also found that Six1 is over expressed in 15 of 20 other cancer tumor types, including colon, lung, bladder and ovarian cancer and leukemia. And when it is over expressed, a cancer is more likely to be highly invasive and recurrent.
 
“All cells in the body have the same genes,” Ford said. “They get switched on or off by proteins in different sequences depending on what the cell is supposed to do. But no one knows why a gene like Six1 gets switched on again or how to turn it off. These are some of the big questions we’re trying to answer.”
 
Six1 over expression is linked to slow-growing tumor initiating cells. Only about 1 percent of tumor cells are tumor initiating cells. The other 99 percent are “child” cells, which are slightly different in makeup and divide aggressively. Current cancer treatments like chemotherapy and radiation kill the fast-dividing child cells, leaving the slow-growing starter cells behind in greater proportion.
 
“If you don’t kill the right cells, the fact that you kill 99 percent of them doesn’t matter in the long term because the cancer will come back, be more aggressive and be harder to treat,” Thorburn said. “We know that Six1 is over expressed in tumors of patients who are resistant to therapy. What we need is a test to use before therapy starts that can tell us this person does or does not have the over expression. That way, we can personalize the kind of treatment each person gets, being more aggressive with those who do have Six1 over expression and perhaps less aggressive with those who don’t.”
 
That's where Wu comes in. She is an expert user of the mass spectrometer, a super-sensitive machine that identifies proteins by their mass/charge. She is developing a rapid, high-throughput test to accurately identify tumors that over express Six1 and determining if the Six1 protein in those tumors is modified in specific ways.
 
No one knows how to kill stem cells or cells with stem-cell-like qualities, like Six1. Thorburn is interested in drugs that stimulate a cell-suicide trigger called the TRAIL signaling pathway—a pathway Six1 stops from working. He thinks that fact may be a clue for developing a drug that will allow us to develop a strategy to get around the block in cell suicide that Six1 causes.
 
Behbakht, who specializes in ovarian cancer, has discovered that tumors with Six1 over expression are harder to remove surgically. With a pre-treatment test, he could decide to give a woman with an over expression of Six1 chemotherapy and radiation before surgery to get a better outcome and, eventually, treat those people with different drugs that are designed to get around the Six1 block or, perhaps even inhibit Six1 itself.
 
“It’s critical that we put together all the disparate and unconnected bits of how this particular part of biology works, to really understand it,” Thorburn said. “But ultimately, we want to help people who have cancer, so we need to be able to translate what we know into new therapies and tests. That’s why having a clinician like Behbakht working on this team is so critical.”
 
Just as the cancer problem must be attacked by prevention, screening and treatment, so must the specific problem of Six1 over expression. With a team of researchers from different disciplines bringing their diversified skills to the table, chances are the problem will be solved faster.
 
“Twenty years ago, we all would be working on our own, and only by chance would you recognize that one of your colleagues was doing work that would take your research in a different direction," Thorburn said. "Because we work in this multidisciplinary environment that is the Cancer Center, we are quicker to learn who we can collaborate with. The hope is your return on investment is much faster progress on the cancer problem.”

Four new Calebresi Scholars named

UCCC has named its second class of Paul Calabresi Clinical Scholars, a three-year training grant program that teaches clinicians and basic scientists to be translational researchers.

Thomas Flaig, MD, assistant professor of Medical Oncology at UC Denver, is a bladder cancer specialist.

Colin Weekes, MD, PhD, assistant professor of  Medical Oncology at UC Denver, is an expert in pancreatic cancer and new drug development.

Rebecca Schweppe, PhD, assistant professor of Endocrinology, Metabolism and Diabetes at UC Denver, is a basic scientist working in thyroid cancer signaling pathways.

Chris Porter, MD, assistant professor of Pediatrics, is a pediatric oncologist interested in new drug targets for acute myelogenous leukemia.

More information about the Calebresi Scholars Program

Hunger, Glodé named Associate Directors

UCCC has added two new associate directors to its executive team.

Stephen Hunger, MD, is now Associate Director for Pediatrics. Hunger is a pediatric oncologist whose practice and research focuses on leukemia. He is professor and chief of Pediatric Oncology, Hematology and Bone Marrow Transplant at the University of Colorado Denver, and director of The Children’s Hospital Center for Cancer and Blood Disorders. Hunger aims to increase basic and translational pediatric cancer research in Colorado.

Michael Glodé, MD, is now Associate Director for Outreach. A specialist in renal, kidney and other genitourinary cancers, he is professor of Medical Oncology at UC Denver. As AD for Outreach, Glodé is leading the creation of a strategic plan to bring UCCC’s world-class oncology expertise and clinical trials to rural areas of the Rocky Mountain region.

"Adding these two positions to our leadership team reflects the new directions UCCC will grow in the coming years," said Paul A. Bunn, Jr., MD, UCCC director. "With Dr. Hunger on board, we will strengthen our relationship with The Children's Hospital and bring more basic and translational pediatric cancer research to our consortium. Dr. Glodé will help us build upon our outreach program, so that we can truly be the comprehensive cancer resource for all people who have cancer in the Rocky Mountain region."