Could you ever imagine sarcoma cancer, with a fairy tale ending? University of Minnesota Professor and cancer geneticist Dr. David Largaespada is working hard to make this happen. Through creative collaboration with others at the University and supported in part by RIS, Dr. Largaespada seeks both to better understand how cancer grows in people and to find new ways to stop it. He is drawn to sarcoma in part because it affects young people, and also because it is understudied. There are “more ideas than ever” being tried against the more common cancers. Dr. Largaespada would like to try these ideas against sarcoma cancer, as well. He expects to see “exciting new research in the near future.” To learn more about these possibilities, click here.

David Largaespada received his Ph.D. in Cellular and Molecular Biology at the University of Wisconsin-Madison in 1992, then did a postdoctoral fellowship at the National Cancer Institute, and finally joined the University of Minnesota in 1996. He holds a joint appointment as Professor in the Department of Genetics, Cell Biology and Development and in the Department of Pediatrics. His cancer research has received national attention, with publication in elite scientific journals and funding support from the National Institutes of Health. Several years ago, through a confluence of happenings, Dr. Largaespada began turning his talents towards sarcoma cancer.

You may have seen headlines about Largaespada’s unique model for identifying the genetic changes that could cause cancer, titled “Sleeping Beauty” because it uses awakened genetic material that was inactive for millennia. If you wish to learn more about this work, just type “largaespada sleeping beauty” into your favorite search engine. You could read for hours! What I will tell you about this work is that it led Dr. Largaespada, ultimately, to us.

When he began using the Sleeping Beauty model, sarcomas were among the first cancers Largaespada found. He looked around the University and saw that others were working with sarcomas. He has long had an interest in pediatric cancers, and felt that sarcomas were understudied. For all these reasons, Dr. Largaespada and his lab began to consider sarcoma. Currently, they have projects underway to apply the Sleeping Beauty model to both osteosarcoma and rhabdomyosarcoma. Through this model, they seek to identify those precise genetic changes in a normal bone or muscle cell that lead to the growth and spread of cancer. Identifying these changes may allow doctors to provide more effective cancer treatments and may provide scientists with new ideas for stopping cancer.

Dr. Largaespada conducts other sarcoma research, as well. One goal is to improve the speed and precision with which potential new treatments could be tested. Largaespada’s lab is working with vectors, which can be thought of as cargo trucks that carry certain types of genetic material into cells. His graduate student Brandon Moriarity is making “a really fancy cargo truck.” If they succeed, they may be able to match up the genetic changes in a particular tumor with the drugs that will offer the best chance for a response. This information can be really important in the clinic, to allow doctors to give the most effective treatments to their patients. The more scientists learn about cancer, the more they understand that each person’s tumor develops in a unique way. The genetic changes within the tumor may be more important than the body part where it first appeared. This may require scientists and pharmaceutical companies to have “a new way of thinking” about how to develop treatments. And perhaps, it could open new possibilities for sarcoma patients.

In 2010, Dr. Largaespada and his colleague Dr. Bridget Charboneau used their RIS grant to build upon literature suggesting that certain fibroblast growth factors may be important in causing rhabdomyosarcoma. When they blocked the action of these growth factors in the lab, the cancer cells did in fact slow down. When they also blocked an insulin growth factor, as well, the cancer cells slowed down even more. Although there are not drugs available right now to achieve all this blocking in people’s bodies, Dr. Largaespada is talking with Dr. Brenda Weigel about the possibilities.

This balance, between basic science research and clinical application, is important to Dr. Largaespada. He firmly believes we need more basic information about the process of cancer development. “On the other hand,” he said, “I’m impatient, like a lot of people.” Against the more common cancers, there are “more ideas than ever before” being tried in people. In case the answer to sarcoma is “already sitting right there,” Dr. Largaespada says: “Let’s try it.”

And trying it, he is. Every other week, Dr. Largaespada meets with a group including physicians Drs. Denis Clohisy, Keith Skubitz and Brenda Weigel and scientists Drs. Logan Spector and Subbaya Subramanian, all working together to find better treatments for sarcoma cancer. At the close of our interview Largaespada said, “I would like to have emphasized the fact that we’ve organized ourselves and created this sarcoma program.” There is a “community of labs” and a collaboration among people. “I expect lots of exciting research in the near future,” he said. And we are hopeful!

Click here for more info on Dr. Largaespada’s research lab

By Christin Garcia

In the three years since she first attended a Rein in Sarcoma event, pediatric oncologist Dr. Nancy McAllister has become deeply engaged in its mission.

As a Children’s Hospitals and Clinics physician, She is connecting her patients with RIS, welcoming patients at the summer Party and partnering with the Red Flags team to increase awareness throughout the community. We are so excited about this collaboration.

From the start Dr. McAllister always wanted to be a pediatric oncologist. She took a slight detour, however, after completing her pediatric residency. Her husband had a medical job in Idaho through his military commitment, and Nancy began practicing as a regular pediatric physician. For a time, she thought the plan for their life might have shifted. She and her husband could have a family and raise their children, while she worked a manageable schedule as a pediatric doctor.

Then one day, she looked at her husband and said, “This is not why I went to medical school.” Her passion for pediatric oncology was still strong. Fortunately, her husband supported this return to her original vision. She took her Fellowship in Pediatric Hematology and Oncology in Utah and was fortunate to study under a great mentor, Karen Albritton. Dr. McAllister gravitated to Dr. Albritton because of their personal connection and Dr. Albritton’s excellence, and also because of Nancy’s affinity for Dr. Albritton’s patients. Dr. Albritton was focused on treating sarcoma, so Nancy too began to develop this specialty.

After Dr. Albritton left Utah, Dr. McAllister led the sarcoma team there for two years. Then a colleague of hers traveled to Minnesota to interview for an open job at Children’s Hospitals of Minnesota. He returned and said to Nancy: “Well, I found your dream job.”

Patients First

Although she had not been looking for a change and could have stayed happily in Utah with her fine team there, Dr. McAllister did go to Minnesota to interview for the Children’s job. She “fell in love” with the opportunity and her husband was happy to move back with her, where they would be closer to their family roots.

What did Dr. McAllister like so much? “The ability to focus on managing patients, first.” Although research and other interests could be pursued if desired, “first and foremost, you get to develop programs and figure out how to manage patients well.” What Dr. McAllister had always wanted to focus on was treating patients. This opportunity offered a great chance to do that, in an outstanding setting.

Since 2006 Dr. McAllister has worked at Children’s, where she serves as a medical oncologist treating pediatric patients with sarcoma. She also focuses on children who have head and neck cancers.

For her sarcoma patients, Dr. McAllister collaborates with the University of Minnesota. Dr. Denis Clohisy and his team perform all the surgeries, since they have so much talent and experience. She works with him to develop the treatment plan for gaining local control, then each does their part. The biggest barrier to their collaboration? A better system for allowing the surgical team to review images and scans taken through Children’s would be great!

Joining the RIS Mission

I was privileged to invite Nancy into the RIS community about three years ago. My neighbor, pediatric oncologist Dr. Joanna Perkins, had been a vital resource for me as I worked to understand my own treatment options for sarcoma in 2007. Once I learned how wonderful RIS was, I shared the Wyckoffs’ interest in deepening our collaboration with Children’s and their patients. So I asked Joanna about this possibility, and she referred me to Nancy

From the start, Dr. McAllister was an engaged participant. In 2009, she and her colleague Dr. Julie Chu attended the Party to celebrate along with survivors. By the 2011 Party, Drs. McAllister and Chu were serving patients and families at the picnic. For 2012, the Children’s contingent will include Drs. McAllister and Chu along with nurse practioners Missy Christensen and Lori Ranney and nurse Cindy Sawtell all of whom work with sarcoma patients.

Their involvement is not limited to the Party. When she was asked to become part of the Red Flags initiative, Dr. McAllister was “excited and enthusiastic to be part of that.” She cares about improving education and awareness, because she thinks “this could save lives.” She and Dr. Chu are collaborating with Theresa Baultrippe, Sue Wyckoff, and several other physicians from the University of Minnesota and elsewhere to develop materials for use with both professionals and lay people.

Children’s has a great outreach program already established through many Minnesota locations outside the Twin Cities metro area. Dr. McAllister would like to bring the sarcoma message out, using this network. Dr. McAllister also appreciated the chance to take part in the recent RIS Stakeholders’ Dialogue meeting, led by Lisa Griebel. “What was amazing to me about that event,” she said, is that a huge group of people came together for a few hours and shared many ideas “in a meaningful way,” and this will translate into a tangible and strategic plan. She has found her time with RIS teams to be well spent. She also found it “so great to have the historical perspective, through the timeline,” for where the group has been.

A Future Dream

Dr. McAllister finds it “such an honor and a privilege to walk through this very difficult time” with children and families facing cancer. She is able to establish deep relationships with people “who are so vulnerable, so needing.” Thankfully, the outcome often can be health and life.

Over time, outcomes are improving for more people. And there is hope for even more improvement, especially since one “beauty of the pediatrics world” is that there is a well-established process for conducting clinical trials that will help develop better treatments. In the meantime, as doctors advance the science, national teams design uniform treatment strategies that use the best science available now. This allows children to receive the best possible care, no matter where they live.

Dr. McAllister seriously hopes the day comes, in a decade or two, when doctors will look back at current practices and say, “I can’t believe we did that.” She hopes there are advances, for example, in better utilizing the body’s immune system to treat itself, or in targeting specific molecular or genetic changes. Certain sarcomas “cry out” for targeted therapies, like Ewing’s sarcoma and synovial sarcoma, given what we know about the tumors.

That first day, driving to the Party, Nancy McAllister and Julie Chu weren’t really sure what kind of an event they would be attending, or what kind of group this was. We are so happy that they found the group meaningful, and have been willing to make such meaningful contributions of their own. Here’s to our continued mission!

By Christin Garcia