Targeting the Cell Cycle and Autophagy Reciprocal Communication Pathways in Sarcoma
Principal Investigator: Erin Dickerson, PhD
Project summary: Sarcomas are tumors of connective tissue that can arise anywhere in the body. They are often challenging to treat because they are extremely rare, preventing the development of beneficial therapies. Angiosarcomas are a type of sarcoma that arise from blood vessel forming cells, and most patients will die within three years of their diagnosis. While these tumors occur in fewer than 300 people each year in the US, a similar tumor, known as hemangiosarcoma, occurs commonly in dogs.
Our research has shown that studying this disease in dogs can help us better understand and potentially treat them in people. Using tumors from dogs being treated with the beta blocker propranolol and the chemotherapy doxorubicin, we compared gene signatures from dogs that showed long-term survival in response to this therapy to dogs that exhibited short-term survival.
Our data showed that dogs surviving more than one year had a specific signature that could be targeted by propranolol. Dogs that did not survive, also contained a very specific signature, and we identified a separate drug that can target these tumors. Our goal is to determine if these two drugs, propranolol and palbociclib, work better together to kill sarcomas. Because similar responses to propranolol have been observed in human angiosarcoma, our findings are likely to translate to human patients. The information obtained from this project will support grant applications to the NIH, DOD, and other agencies. Successful results will help us to refine our approach and guide the development of other treatment combinations.
Michelle Kolling, End-of-Life Doua, Grief Coach, and founder of Held is conducting a grief-related research project and needs your input!
If you or someone you know has experienced the life-changing loss of a spouse, partner, child, close family member, or friend and is curious about the grief journey and how they are personally experiencing grief, Michelle would love to hear your story.
In exchange for sharing your story and answering a few questions, you will receive a complementary Grief Coaching Session where you will discover a deeper connection to yourself and your person. No matter where you are on your grief journey, whether it’s been 6 months or 10 Years, LET’S CONNECT.
It might seem strange that Rein in Sarcoma supports dog cancer research but there’s a good reason.
Canine hemangiosarcoma, a type of dog cancer, has been known among veterinarians as one of the most vexing diseases to treat.1 It is highly aggressive, fatal, and may not make itself apparent until a seemingly healthy dog collapses. Once a cancerous tumor is found, it’s not uncommon for a dog to die within 6 to 8 weeks.2
About 50,000 dogs each year are diagnosed with hemangiosarcoma according to a 2017 Public Library of Science research article.3 The cause is unknown, but it’s seen in pet dogs all over the United States and worldwide. Hemangiosarcoma may occur in any breed at any time, but it’s mainly diagnosed in older dogs, usually between 9-12 years old.4
So why did Rein in Sarcoma award a grant in support of canine hemangiosarcoma research this year? Because it turns out that dogs benefit from what researchers have learned about treating a similar cancer in humans known as angiosarcoma. And when researchers capture data on how dogs respond to hemangiosarcoma treatment, that data is then applied back to how angiosarcoma may be treated in people.
We talked with Rein in Sarcoma grant recipient Erin Dickerson, Ph.D. She’s an associate professor of oncology and comparative medicine in the Veterinary Clinical Sciences department at the University of Minnesota.
RIS: How much of an overlap is there between canine hemangiosarcoma and human angiosarcoma?
Dickerson: They are virtually identical in their appearance and progression. New technology has helped us identify some differences, but there are a lot of similarities.
RIS: So, you’re doing comparative research. You’re studying what happens to pet dogs who have been diagnosed with cancer by a veterinarian, and it’s the owners, and vets who are taking the initiative to treat the dog. What can you learn from these dogs?
Dickerson: We can learn a lot from dogs as a model for sarcomas because they have a compressed lifespan. We are able to treat a dog and determine the outcome in months or a couple of years. In contrast, a study on human patients could take years or decades.
Since so many dogs do get sarcoma, there’s a large enough pool to do valid studies. In contrast, the number of people who get sarcoma is much smaller — it’s a challenge to find enough patients with sarcoma who meet the criteria for a clinical trial. So, what we do is use the data we get from studying the dogs and apply that to our questions and results regarding human sarcoma.
RIS: How do you and the dog owners connect?
Dickerson: We do a lot of outreach and often participate in local events. We go to the Rein in Sarcoma picnic each year. Even there, many do not know that dogs can get cancer, or specifically sarcomas, or that dogs are being studied to help with treatments for humans with cancer. We also go to the State Fair and participate in programs at the Science Museum – they host a Goldy vs. cancer event each year.
A lot of dog owners aren’t aware that dogs can get cancer. Many owners are shocked to discover cancer in their pet dog. An owner can bring their dog to the clinic at the University of Minnesota College of Veterinary Medicine (CVM) for care. We often run clinical trials to determine if a new treatment might work better for hemangiosarcoma or other sarcomas. Depending on the trial, a lot of expenses may be covered. The trials that we run are very similar to those for people where certain standards and guidelines need to be followed.
We call hemangiosarcoma the ‘silent killer’ since many dogs don’t show any signs of this cancer until it has progressed. At this point, it can often be too late. So, we’re trying to get the word out to dog owners about what to look for so they can work with their veterinarian to can catch the disease early.
RIS: What sparked your interest in dogs and cancer?
Dickerson: I got started while studying breast cancer in a lab when I was in college. Later, I went to graduate school and started studying something totally different. After I got my Ph.D. I wanted to get back into cancer research.
As a researcher, I found out about the prevalence of hemangiosarcoma in dogs, and that it’s been a problem in veterinary medicine for a long time. In line with human angiosarcoma, there weren’t any good treatments. I’m a dog lover so I felt like this was a space where I wanted to make a difference. Hemangiosarcoma is a complex disease. We may not find a cure in my lifetime, but I hope to make a difference and improve the lives of dogs with this disease. I also hope that we can help people diagnosed with angiosarcoma.
RIS: How did you get acquainted with Rein in Sarcoma?
Dickerson: One of my collaborators at the University of Minnesota, Dr. Jaime Modiano, told me about Rein in Sarcoma when I first arrived at the university in 2009.
Dr. Modiano has also been the recipient of Rein in Sarcoma grants. It’s amazing how far our research has come — more has been learned about hemangiosarcoma in the last decade than in the previous 30-50 years.
Researchers are building a perpetual cycle of learning from dogs to help humans, then learning from humans to help dogs and back again. Little by little, we’re helping both dogs and people.
RIS: How can RIS readers support the research?
Dickerson: The best way to help is by getting the word out. Let people know that dogs can get sarcomas, and there are treatments that can help. Building awareness of the comparative medicine approaches is also something that will help both dogs and people.
If there are veterinarians and pet owners looking for more information, they may appreciate a podcast we did with Morris Animal Foundation. It can be found on the foundation website under the January 2023 “Fresh Scoop” Episode 52: New Ideas on Hemangiosarcoma in Dogs.
Rein in Sarcoma’s Board approved a $50,000 research grant to the University of Minnesota.
The University solicited requests for funding proposals from their researchers, blindly ranking them according to national standards, and then recommended the proposal submitted byErin Dickerson, PhD.
Project Title: Targeting the Cell Cycle and Autophagy Reciprocal Communication Pathways in Sarcomas
Principal Investigator: Erin Dickerson, PhD Associate Professor, Veterinary Clinical Sciences
Institution: University of Minnesota
Amount: $50,000
Project Summary:
That autophagy and cell cycle signaling pathways regulate specific subtypes in hemangiosarcoma, and combinatorial approaches targeting these pathways will enhance antitumor responses. Our goal is to identify pathways that drive angiosarcoma progression and to develop new treatment options to improve patient outcomes. By analyzing tumors from dogs enrolled in an ongoing clinical trial, we have identified targetable subtypes that have allowed us to design a combinatorial treatment strategy that may translate to human patients diagnosed with angiosarcoma. Data from this project will be used to support grant proposals to rigorously characterize the identified subtypes and to refine the development of our approach.
On Friday, March 31 Rein in Sarcoma hosted with Dr. Brenda Weigel of the Masonic Cancer Center our sixth annual Sarcoma Research Symposium featuring speakers who have received grants funded by the work of our community. After a light breakfast and warm welcome from Dr. Weigel, twenty-seven online participants and over forty in person guests ranging from graduate students, patients and families as well as to tenured medical professionals listened to:
Dr. Erin Dickerson, UMN “Using Propranolol to Generate Anti-Tumor Microenvironment”
Dr. Jaime Modiano, UMN “Identifying and Characterizing the Cells that Create the Primary and Metastatic Sarcoma Niche”
Dr. Kris Ann Schultz, Childrens Minnesota Hospitals & Clinics “DICER1 Related Sarcomas”
Dr. Berkley Grider “Identification of New Strategies to Therapeutically Intervene for Rhabdomyosarcoma by PAX3-FOX01 and MYCN”
Dr. Thanh Ho, Mayo Clinic “Clinical and Laboratory Tools to Evaluate Treatment Tolerability in Older Patients with Soft Tissue Sarcoma”
Lunch followed and we shared boxed lunches together talking to participants, and attendees in the spacious atrium and first floor café area. Thanks to Dr. Kelsey Becklin we followed up with an exceptional laboratory tour of the Dr. Beau Webber and Dr. Branden Moriarity labs where we saw osteosarcoma cells and Ewing sarcoma cells under microscopes. We learned about the equipment in the lab as well as methods practices and procedures to create new treatments for sarcoma. Stay tuned for our 2024 research line up. Please join us next year and participate in the work of RIS to keep improving outcomes.
Our gratitude for the supportive event work of: Emerson Fuller, Kayli Britos, Micki Driers, Katy Engelby, Dr. David Largaespada. We cheer on the work of graduate students, physicians, mentors, researchers and community members together.
We invite you to join us for the Minnesota Sarcoma Research Conference 2023: Progress and Promise, a hybrid event sponsored by Rein in Sarcoma (RIS) and the Masonic Cancer Center, University of Minnesota The Progress and Promise Sarcoma Research Conference is a forum for researchers to share their findings to RIS stakeholders and students and further the collaboration among RIS-sponsored researchers.
This year, you can attend virtually or in-person at the University of Minnesota Twin Cities campus. Some sessions may be recorded and will be available on YouTube after the event, but we recommend attending live as some in-progress research updates cannot be posted.
This event will also include a lab tour and networking opportunities.
This event will also include a lab tour and networking opportunities.
