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

University of Minnesota Professor Jaime Modiano is a dog doctor, whose passion for treating his animal patients may translate into new medicine for you. Dogs get sarcoma cancers, naturally, at a much higher rate than people do. They also have much shorter life spans than people. We can learn a lot by studying dogs, and can quickly determine which new treatments may be best, for them and for us. University scientists, medical doctors and veterinary doctors are working together on many exciting research projects, including those for angiosarcoma and osteosarcoma. Dr. Modiano says: “I’m doing something I love to do,” which may end up helping people and their pets. To learn more about exciting sarcoma collaborations, some inspired and funded by RIS, keep reading!

Dr. Modiano completed his training in veterinary medicine and received a PhD in immunology at the University of Pennsylvania in 1991. He completed a residency and fellowship in Colorado, then moved to Texas A&M for several years. From 1999 to 2007 he worked in Colorado, serving as a senior scientist in cancer research and an Associate Professor of Immunology. Dr. Modiano misses the gorgeous mountains and dry air in Colorado, but also loves his new work in Minnesota. In 2007 he joined the College of Veterinary Medicine here, where he serves as Professor of Comparative Oncology and as Director of the Animal Cancer Center and Research Program.

“I am a dog doctor, I am proud to be a dog doctor.”

Dr. Jaime Modiano

Dr. Modiano began our interview by emphasizing that “I am a dog doctor, I am proud to be a dog doctor.” He studies naturally occurring cancers that arise spontaneously in dogs. Dogs are much less likely than people to get breast cancer or prostate cancer. “Dogs don’t smoke,” and they don’t really get lung cancers. Their diets are a bit different, so they don’t get a lot of the gut cancers humans do. Dogs do get cancer, though, and the cancers they are much more likely to get are blood cancers and sarcomas. These cancers are “very rare in people, and very common in dogs.” This gives doctors an opportunity and a question: “Can we use the tumors happening spontaneously in dogs to help us answer the questions” why people get cancer, and what doctors can do about it?

In many respects, the answer is a resounding YES. For example, other than the life stage at which it occurs, osteosarcoma in dogs is “virtually identical” to the disease in people. And in dogs, it may be much easier to figure out what is driving the problem. There are many steps on the way to a cancerous tumor. First, one cell needs to “become bad.” Then this cell needs to acquire the ability to outcompete its neighbors and grow out of control. Many different things can go wrong along the way, and when scientists look at many tumors – even of the same cancer type – they see hundreds of different genetic mutations. What they really need to know is: Which are the really bad actors? What should be our targets? Because people have exercised control over dog breeding, there are discrete breeds with more isolated, narrower gene pools. This gives doctors a better chance to find important traits that really drive cancer growth and spread.

Some time ago, Dr. Modiano and his colleagues began approaching this question in a slightly different way: they decided to “let the tumor tell us what matters.” They identified molecular genetic “signatures” that tended to appear in one of two different ways in each bone tumor. When they looked at the two groups of animals to see if there were any other differences between them, besides the genetic signature of their tumor, they discovered that these signatures correlated with survival time. One signature occurred in a group that did very poorly; the other signature occurred in a group that did better. The team then applied their bone cancer signature test to other groups of dogs or people and found that separation into two similar groups was there, every time.

Jaime is married to Dr. Michelle Ritt, a board certified specialist and Clinical Associate Professor of Medicine at the University of Minnesota. They share their home with Logan and Quetzal. The researchers think they know what cellular component is responsible for causing the really bad outcome, but more testing is needed. With this year’s RIS grant, Dr. Modiano will test to see if different variations of the gene he thinks is so important really will cause differences between the two bone cancer signatures. If the answer is yes, “then we have a target” for new drug treatments.

With an earlier RIS grant, Dr. Modiano studied angiosarcoma growth and development. He was able to build upon previous work to strengthen the evidence for “very select survival-related effects” associated with certain cancer stem cells. In other words, scientists may be able to predict which tumors will develop rapidly and spread aggressively by looking to see whether or not they have these few certain kinds of cells. Figuring out how these particularly lethal cancer cells stay alive, even when they should be marked for death by our body, also may give doctors new drug targets.

For both projects, small RIS grants have allowed Dr. Modiano to build upon past research and strengthen the evidence for major grant requests, which ultimately may leverage scientific experiments into better clinical knowledge and successful cancer treatment, for our dogs and for their people. And once again, we see collaborative energy stirring at the University, leading scientists with different backgrounds and specialties to work together in asking important questions and pursuing creative answers. For this support, Dr. Modiano is “very excited and very grateful.” For the work, we are excited and grateful as well.

By Christin Garcia

To learn about the Modiano Lab at the University of Minnesota, click here.

Dr. Scott Okuno is an Oncologist at the Mayo Clinic in Rochester, Minnesota, where he treats patients who have sarcoma. He works with a team of people who have different specialties, “a good group of people,” who are “learning all the time” and who put their knowledge together to decide how best to treat patients.

He is a Professor of Oncology, and in his academic research, he collaborates with physicians across the Midwest to design studies that will help doctors find better treatments for their patients. Dr. Okuno also serves in the Rein in Sarcoma Advisory Board, and in the Board of Directors.

Setting the Course

Dr. Scott Okuno grew up in Prospect Heights, Illinois. He went to St. Olaf College, and tells us: “there I met a gal who was from a small town in Minnesota, Kasson. We fell in love. We got married.” So, after completing medical school in Illinois, Dr. Okuno and his wife moved back to Southeast Minnesota to be near her home town. Dr. Okuno completed his Residency at Mayo, and also his Fellowship in Hematology and Oncology. He joined the Mayo Clinic staff in 1996 and has worked there ever since.

Scott Okuno, MDDr. Okuno knew “somewhere along the way” that he wanted to be a doctor. Being “engaged with people” interested him. In a sense he continued the family profession, as his dad was a pathologist and his mother a nurse.

When Dr. Okuno began working at the Mayo Clinic, he joined practice with a senior physician who was an expert in sarcomas. There was a need for a new doctor to train with this physician for several years, then carry on in his place. Dr. Okuno took on this role. As he began treating sarcoma patients, he started liking this work more and more.

At Mayo, an oncologist like Dr. Okuno does not treat patients alone. There is a team of people, a good group of people, who get to know each other and work together. The doctors have different specialties, and they put their knowledge together to decide on the best treatment for their patients. It’s a “happy environment,” which makes him want to stay. Every week, every day, he learns more. He says, “we’re learning all the time.”

A Goal for Sarcoma Treatment

For sarcoma, what doctors would really like to learn is better treatment options. It is hard to conduct clinical studies in sarcoma, because there are so few people who get the disease and there are so many variations within the disease. Sarcoma is not just one cancer, and the different types respond to medicines differently. But the Mayo doctors, along with other major academic centers in the Midwest – including Rein in Sarcoma partner University of Minnesota – are collaborating to design studies that will provide useful new information more quickly. By pooling their resources and sharing patient information, they can get answers more effectively.

Joining with the Rein in Sarcoma Foundation

Dr. Okuno was introduced to Rein in Sarcoma’s work when he got a call from Dr. Keith Skubitz, asking him to review proposals for the research grants being awarded by RIS. He was interested to read about all these projects. At about the same time, he received a request to meet with RIS President Pete Wyckoff, to discuss a more active role for him and his colleagues. One wintry day Pete did drive down, with sarcoma survivor Kevin O’Keefe, and the three men talked

Dr. Okuno also was encouraged by two patients who had been touched by RIS. He realized that doctors alone “can’t do it all.” Doctors are able to see their patients for a half hour or an hour, and in that short touch point must discuss a potentially life-threatening illness or body-altering experience. Patients then must go home to live and function within their families and communities. There is a need for an organization to connect these patients and their families with good information and with others who have faced the same things.

He found RIS to be passionate, organized, and focused on an important message. He has consulted with the Red Flags team to provide accurate medical information. In July 2014, he attended his first-ever Party in the Park. “What a beautiful event,” he says. The weather was awesome, the crowd was great, and the memorials and luminary readings provided touching moments.

A Hope for the Future

Working with his Mayo team, and in collaboration with others, Dr. Okuno would like to continue conducting the research studies that may improve outcomes for sarcoma patients. And here is a goal we all can embrace.

University of Minnesota Associate Professor and orthopedic surgeon Christian Ogilvie chose medicine so he could practice science, while working directly with people. He likes teaching people, educating patients. And he likes to fix things. He appreciates the chance to make a big difference in someone’s life, in a moment. To restore them, perhaps, to what they could do before.

Dr. Ogilvie has been a great asset for RIS. He has embraced our education mission: teaching residents about sarcomas, speaking to medical students through the RIS Maudlin Sarcoma Scholars Program. Dr. Ogilvie has also served in the RIS Board of Directors.

Family Beginnings

Christian Ogilvie’s father was a doctor. A spine surgeon, who spent years at the University of Minnesota and operated on many people with scoliosis. Even as a high school student, Dr. Ogilvie was drawn to the chance for sudden change. To take a crooked spine and make it straight, all in one setting.

In college, Dr. Ogilvie had the opportunity to do service work. He found it “really rewarding to work directly with people,” and he wanted to include this type of feeling with his professional work. He liked science, and decided medicine would be a great career. He returned to Minnesota to attend medical school here, at the University.

Before and during medical school, Dr. Ogilvie worked in Dr. Clohisy’s lab. Through this work he became interested in tumors. Although he considered pediatric medical oncology for a time, ultimately Dr. Ogilvie wanted to “intervene directly.” He liked performing surgical procedures, and he wanted to take the cancer out. So he took his residency in Orthopaedic Surgery, then a fellowship in Musculoskeletal Tumor Surgery at the University of Toronto.

Geography

Upon completion, Dr. Ogilvie moved to the University of Pennsylvania, where he was an Assistant Professor and a surgeon. He developed a busy practice, focused on tumors. In one single year, he saw 400 individual cancer patients.

When Dr. Clohisy was becoming Chair of the Orthopaedic Surgery Department at the University, he called to recruit Dr. Ogilvie back to Minnesota. In 2009, Dr. Ogilvie returned. He had met his wife here, and the two of them felt this was a good place to raise children.

At Minnesota, Dr. Ogilvie’s practice still involves tumors. He focuses on sarcoma, but does other things as well, including major trauma. He drew many connections between the two. Like sarcomas, fractures can occur anywhere in the body. Both trauma surgery and sarcoma surgery may involve bones and joints. And, you will not be surprised to hear that trauma surgery calls to Dr. Ogilvie because it offers the chance to take a crooked, broken bone and straighten it out, all in one setting; to place a plate on it; to help it heal.

You may be surprised to learn that unlike many other tissues in the body, bone really can heal. Cleanly, completely, and without a lot of scar tissue getting in the way of good function. If the conditions are right, if you give it enough time, bone will replace itself and be almost like new. Often, people can go back to doing just about everything they were doing before, because their bone will go back to doing what it was doing before.

Education

Medical students and residents may not get much education about sarcomas, even today. Through his practice, Dr. Ogilvie has seen the patients who don’t get diagnosed. Sometimes, an incomplete surgery by a non-cancer specialist will require a second revision surgery, bigger than it would have needed to be.

Dr. Ogilvie talks to people about sarcomas. He has presented at Grand Rounds for medical students twice, through the Wyckoff Sarcoma Scholar program, and expects to do this again. He speaks to orthopedic residents about sarcomas, since people will show up in their offices with lumps and bumps and pains. Most will be benign and harmless, but some will be cancer. He wants people to consider the cancer, before they cut.

What is hard?

The hardest thing about Dr. Ogilvie’s job “is probably telling someone their kid has cancer. That’s difficult.” The parents are kind of helpless, and they have so many questions. Most times, they worry a lot. The second hardest thing? Telling someone they have metastatic disease. The third? Telling someone they have cancer.

It is rewarding, though, when you have the ability to tell people you can take out the cancer and they’ll be fine. When you can “educate them a little bit, make some plans” and attack the tumor. Or when a person has pain from cancer in their bone, and has trouble walking, and surgery can help them feel better. When you can “help out with the quality of life.”

There are lots of opportunities for constructive outcomes. Sometimes, these come in surprising forms. Allowing someone to go home, for even a few days, may be a victory.

We are thankful that Dr. Ogilvie has decided to embrace these challenges, here.

By Christin Garcia