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Light Bulb Moments Illuminate Multiple Myeloma Program

When it comes to multiple myeloma patient care and research, the UW Carbone Cancer Center’s (UWCCC) bench to bedside approach is not unique – all comprehensive cancer centers take this approach.

What is unique? UWCCC’s relatively small size has actually been a boon to collaboration, allowing an interdisciplinary group of physicians and researchers to create a formidable team. Together, they have made great strides in multiple myeloma research and care, with even more on the horizon.

“Many larger universities really struggle to get people from different disciplines together,” said Natalie Callander, MD, professor (CHS), Hematology, Medical Oncology and Palliative Care. Dr. Callander is a hematologist who specializes in treating multiple myeloma patients. “Here, we have PhDs and physicians and pathologists working together, and our different viewpoints enhance everything we do.”

Multiple myeloma is a blood cancer that affects 30,000 new patients each year. For most patients, there is no cure; chemotherapy and bone marrow transplants can lead to remissions, the lengths of which vary based on the number of prior treatments and how a patient responded. Not even ten years ago, the median survival was five years. Today, it is around nine years.

“That’s very good news, but myeloma drugs are very expensive,” Dr. Callander said. “I’m interested in asking, how do you treat patients in a medically effective but cost effective way?”

Prior to 2003, there was relatively little research happening at UWCCC on the disease. However, several generous and forward-looking patients with myeloma established the Trillium Fund to support myeloma research at UWCCC.

Dr. Callander arrived at UW-Madison in 2004 and was introduced to UWCCC members Shigeki Miyamoto, PhD, professor, McArdle Laboratory for Cancer Research; Alan Rapraeger, PhD, professor, Department of Human Oncology; and Peiman Hematti, MD, professor, Hematology, Medical Oncology and Palliative Care.

Dr. Callander said Drs. Miyamoto, Rapraeger, and Hematti were not specifically working on multiple myeloma at the time she arrived, but all were conducting research that was closely linked to the disease.

“Shigeki was originally studying a breast cancer pathway that is dysregulated in 90 percent of myelomas,” she said. “Alan had for years been studying a signaling protein called syndecan-1, which turns out to be on nearly every myeloma cell, and Peiman had expertise in stem cells and macrophages. We sat down and said, ‘Let’s pool our strengths and see what we can come up with.’”

Ten years ago, the team developed what turned out to be a game-changing plan: the development of a myeloma tissue bank. In typical tissue donations, patients consent to donate extra biopsy tissue, beyond what is needed for their treatment. For the myeloma bank, patients generously consent to a second, painful bone marrow biopsy. This second tissue sample is then made available to UWCCC researchers and linked to patients’ clinical outcomes.

“That was gold for us,” Dr. Miyamoto said. “With patient samples, we can learn how they are so different from patient to patient, which we cannot do nearly as well with established cell lines in the lab.”

Dr. Miyamoto uses these samples to investigate how the tumor microenvironment influences cancer development and progression. He has found that the non-cancerous, healthy cells that interact with the myeloma cells contribute to chemotherapy resistance. He and UWCCC member David Beebe, PhD, John D. MacArthur Professor & Claude Bernard Professor, College of Engineering, have developed a microfluidics device that mimics the tumor microenvironment. They can test drug combinations on tissue samples and predict, in a matter of days, which next therapy is likely to benefit the patient.

Both the team approach and access to the myeloma tissue bank contributed to bringing Fotios (Fotis) Asimakopoulos, MD, PhD, associate professor, Hematology, Medical Oncology and Palliative Care, to UW-Madison in 2010. He is a physician-scientist who treats and studies multiple myeloma.

“I came to UW because I could clearly see the potential for great work and rapid progress,” Dr. Asimakopoulos said. He brought with him additional invaluable resources: a mouse model of multiple myeloma, the expertise to work with it, and a research focus on cancer immunotherapy. His group is looking for ways to mobilize the immune system to attack cancer cells. They also want to understand why cancer cells are protected from chemotherapy, which complements Dr. Miyamoto’s work on drug resistance.

In addition to lab research, Dr. Callander, Dr. Asimakopoulos, and their newest colleague Aric Hall, MD, assistant professor (CHS), Hematology, Medical Oncology and Palliative Care, lead UWCCC’s myeloma clinical research team. That team develops their own clinical trials and partners with other cancer centers or pharmaceutical companies to bring national clinical
trials to Wisconsin. These trials give patients access to breakthrough treatments, helping advance multiple myeloma patient care.

“I’m thrilled to be at UW,” Dr. Callander said. “We really feel like we’ve built something special here.”

Editor's note: The Trillium Fund supports myeloma research at the UW Carbone Cancer Center. To make a gift to the Trillium Fund, visit the www.supportuw.org/giveto/trillium. 


Additional multiple myeloma investigators at UW Carbone Cancer Center:
Peiman Hematti, MD
Professor, Department of Medicine, Division of Hematology, Medical Oncology and Palliative Care
• Dr. Hematti’s group was the first to study how some noncancerous cells, including bone marrow stromal cells and macrophages, interact with myeloma cells in the tumor microenvironment.
• In addition to treating myeloma patients as a bone marrow transplant physician, he is the Director of the University Hospital clinical hematopoietic cell processing lab that is producing personal cellular vaccines for one of Dr. Callander’s clinical trials.

Alan Rapraeger, PhD
Professor, Department of Human Oncology
• Dr. Rapraeger’s research group studies how a receptor, syndecan-1, allows myeloma cells to invade, suppress immune cell infiltration and induce the formation of new blood vessels that bring a blood supply to the tumor.
• They are designing “synstatin” drugs to block syndecan-1, expecting that the synstatins will prevent tumor growth, cut off their blood supply and enhance the immune recognition of the tumors.

Jing Zhang, PhD
Centennial Professor of Oncology, McArdle Laboratory for Cancer Research
• Working closely with Dr. Asimakopoulos, Dr. Zhang and her research group are developing a new mouse model of multiple myeloma.
• These mice closely model highly malignant multiple myeloma and could be used for testing potential new therapies or studying drug resistance to current therapies.

Erin Costanzo, PhD
Associate Professor (CHS), Department of Psychiatry
• Dr. Costanzo is a psychologist who studies the links between cancer, mental/behavioral health, and the immune system.
• Her work has shown that multiple myeloma patients who have undergone bone marrow transplant and report having strong social support showed an increase in both immunity and anti-myeloma biomarkers and a decrease in inflammatory biomarkers, suggesting that paying attention to and helping patients bolster their support may improve health and outcomes.


- this feature story was contributed by Sarah Perdue, university relations specialist, UW Carbone Cancer Center.