Sarcoma survivor and Rein in Sarcoma volunteer, Miranda Mead, has served for the past three years as a Peer Reviewer for the United States Department of Cancer Peer Review Panel. Miranda works with leading researchers, scientists, and oncologists from around the country to determine which cancer research proposals they fund.
This year, Miranda was asked by Dr. Donna Kimbark, Program Manager for the CDMRP, to serve as the speaker for at the Congressionally Directed Medical Research Programs (CDMRP) meeting on Friday, August 27. Dr. Kimbark has managed research funding programs for autism, multiple sclerosis, cancer, and bone marrow failure syndromes. Miranda opened with a Moment of Silence presentation to remind everyone of the importance of the work and the many lives affected.
The CDMRP, created in 1992 via a Congressional appropriation, fosters novel approaches to biomedical research to support the needs of the American public, the military, and Congress.
The CDMRP funds high impact, high risk and high gain projects that other agencies may not fund. All of the programs managed by the CDMRP share the common goal of advancing research, solutions that will lead to cures or improvements in patient care, or breakthrough technologies and resources. The CDMRP strives to transform healthcare through innovative and impactful research.
Thank you, Miranda, for being a part of this team and raising awareness about sarcoma cancers.
Rein in Sarcoma has been asked by KJT Group to promote a study they are conducting for people living with PEComa. They are looking for PEComa patients who may be willing to share their experiences. KJT Group will be conducting 60 minute virtual discussions with qualified patients. By sharing feedback with their research team, you can help improve treatment experiences and outcomes of others like you.
If you have been diagnosed with PEComa and would be willing to discuss your experiences with KJT, complete the survey. You will be asked a few questions about your background and experience. If you qualify for the study, there will be the opportunity to immediately schedule an interview.
Blake Hastings, RIS Board Director, Melissa Davies, Development Director, Dr. Brenda Wigel (UMN), Eric Lien, RIS Board Vice President, Janelle Calhoun, RIS Executive Director, and Tom Boardman, Development Committee Chair.
Rein in Sarcoma’s Board approved a research grant to the 2021 University of Minnesota at its January meeting. The number of grants were reduced based on buget decisions made in the spring of 2020. The University solicited requests for funding proposal from their researchers, blindly ranked them according to national standards, and recommended the proposal by Dr. Jaime Modiano, School of Veterinary Medicine to the RIS Research Committee.
We are pleased to fund this research, and look forward to a presentation on findings at the Sarcoma Research Symposium in 2023. Dr. Modiano has received Rein in Sarcoma research funding in prior grants. He shares with us:
“The data from our previous Rein in Sarcoma grants has helped us secure almost $6M in external grants for sarcoma research from the federal government (NIH and DOD), the state of Minnesota, and animal health foundations. These grants have been instrumental in helping us to complete work that is reported in numerous peer reviewed scientific articles as well as in lay articles. We are extremely proud of our return on investment from this meritorious program.”
Identifying and Characterizing the Cells that Create the Primary and Metastatic Sarcoma Niche | $50,000
Jaime Modiano, VMD, PhD
Jaime Modiano, VMD, PhD – Principle Investigator, Professor of Veterinary Medicine & Research
Aaron Sarver, PhD – Co-Investigator, UMN Medical School Assistant Professor Institute for Health Informatics
Sarcomas, or tumors of connective tissues, are challenging to treat because they tend to invade deep into tissues. This behavior makes it virtually impossible to remove all of the cancer even with very aggressive treatments. But some sarcomas pose even greater challenges because they spread to organs far from the primary tumor. In these tumors, the distant spreading, called metastasis, is the eventual cause of death for patients.
Aaron Sarver, PhD
Primary tumors of bone (osteosarcomas) and of blood vessels (angiosarcomas) are two highly metastatic sarcomas. The assumption with these cancers is that malignant cells have already spread by the time they are diagnosed. Because of this, patients receive extremely intensive therapies that can have severe side effects. Even so, more than half of patients with bone cancer and with blood vessel cancers die from their disease within about 10 and 3 years, respectively. For bone cancer, a 10-year survival might seem acceptable, were it not for the fact that this cancer mostly affects children, adolescents and young adults. It is well accepted that osteosarcomas and angiosarcomas spread through the blood circulation. This has led many investigators to search for tumor cells in the blood. We pioneered this approach for angiosarcoma almost two decades ago. But recent technological improvements provide opportunities to understand how and why the tumor are able to travel to distant sites. In addition, we are now able to find the chaperones that help them colonize new organs and create homes where they can thrive.
Osteosarcomas and angiosarcomas are quite rare in people. On the other hand, both are very common in dogs. We have shown that studying these diseases in dogs can help us better understand, diagnose, and potentially manage them in people. Here, we will use the same approach, studying tumor cells in the circulation of dogs with osteosarcoma and angiosarcoma. We will apply a technology called single cell sequencing. We have already developed methods to find and recover these cells from simple blood samples. Our goal is to determine how tumor cells and their chaperones alter their behavior to support the process of metastasis. The information we obtain from this project will support grant applications to the NIH, DOD, and other agencies. This line of work will help us to identify the cells that are responsible for sarcoma metastasis. In turn, the results will guide development of tests for early detection and to monitor disease progression. And finally, our efforts will provide insights to design new, safe and effective therapies to manage or prevent metastasis.
Charlie Gerk with wife and RIS volunteer, Danielle Gerk
Sarcoma survivor and RIS volunteer Charlie Gerk recently participated in the evaluation of research applications submitted to the Peer Reviewed Cancer Research Program (PRCRP) of the Congressionally Directed Medical Research Programs (CDMRP).
Charlie was nominated for participation in the program by Rein in Sarcoma. As a consumer reviewer, he was a full voting member, (along with prominent scientists) at meetings to help determine how the $110 million appropriated by Congress for Fiscal Year 2020 will be spent on cancer research.
About the PRCRP program
Consumer reviewers are asked to represent the collective view of patients by preparing comments on the impact of the research on issues such as diagnosis, treatment, and quality of life. When commenting on serving as a consumer reviewer, Charlie said that, “he was heartened to know so many dedicated people are working hard on cures for sarcoma”.
Consumer advocates and scientists have worked together in this unique partnership to evaluate the merit of research applications since FY09. COL Sarah B. Goldman, Director of the CDMRP, expressed her appreciation for the consumer advocates’ hard work. “Integrating consumer perspectives into our decision-making process brings energy and focus to our research programs. Patients, caregivers, family members, and advocates help us keep our efforts centered around what is truly important to those impacted. We very much value this critical input from our consumers who help ensure that CDMRP’s work remains critical and relevant,” she said.
Scientists applying propose to support and promote high-impact research for cancer prevention, detection, treatment, quality of life and survivorship, and decreasing the burden of cancer on Service members, their families and the American public. The PRCRP fills important gaps not addressed by other funding agencies by supporting groundbreaking research while encouraging out-of-the-box thinking.
If you are interested in learning more about participating in the CDMRP’s Scientific Peer Review Panels, please contact Janelle Calhoun, Rein in Sarcoma’s Executive Director at (763) 205-1467 or execdirector@reininsarcoma.org.
Rein in Sarcoma has awarded $40,000 in new sarcoma research grants to Children’s Minnesota and the Mayo Clinic. The grants were announced during the recent virtual Fall Fundraiser. The RIS Research Committee reviews the top proposals brought forward by each institution’s evaluation committee, and in turn recommends final awards to the RIS Board of Directors for approval.
Children’s Minnesota
“DICER1-related Genitourinary Sarcomas” | $15,000
Dr Kris Ann Schultz
Principal Investigators: Kris Ann P. Schultz, MD, pediatric oncologist
Lay Summary: DICER1-related sarcomas include pleuropulmonary blastoma (PPB), renal sarcoma, ovarian, cervical and uterine sarcoma, and a newly-described tumor type, PPB-like peritoneal sarcoma which may arise from peritoneal structures. We have preliminary data suggesting that in PPB, quantitation of circulating tumor DNA bearing DICER1 “hotspot” mutations may provide a way to measure tumor burden and provide a strategy for early diagnosis, especially for children with recurrent disease. In this proposal, we will leverage our prior Rein in Sarcoma funding and R01-funded existing PPB-related research activities and extend these to include additional DICER1-related sarcomas. Development of this additional collated data source is the next necessary step toward our goal of validating ctDNA for clinical use in children and young adults with DICER1-related sarcomas.
Mayo Clinic
“Targeting the Immune Checkpoint B7-H3 for the Treatment of Rhabdomyosarcoma.” | $25,000
Principal Investigator: Dr. Fabrice Lucien-Matteoni, PhD, Senior Research Fellow in Urology Co-Investigators: Dr. Haidong Dong, MD, PhD, Professor of Immunology, a world-renowned immunologist and Dr. Akilesh Pandey, PhD, Professor in Laboratory Medicine and Pathology and Director of the Proteomic
Lay Summary: Rhabdomyosarcoma (RMS) is the most common soft tissue tumor in children, with nearly 20% of children presenting with locally aggressive and/or metastatic disease. A fundamental problem with this disease is the lack of effective and tolerable therapeutic regimens. Current protocols including surgery, radiotherapy and chemotherapy are extremely toxic and may lead to multiple deleterious long-term effects. Moreover, a significant percentage of patients tends to relapse and for those patients, life-expectancy is less than 5 years.
Our group is dedicated to help develop more effective and more tolerable treatments for rhabdomyosarcoma. In the past year, we have screened for proteins enriched in RMS tumors compared to normal muscle in the intent to identify new therapeutic targets for the treatment of RMS. We have discovered the molecule B7-H3 as an important mediator of tumor progression. B7-H3 protects tumor cells from being attacked by immune cells. We have found that loss of B7-H3 expression leads to tumor regression through an effective antitumor immune attack. In this proposal, we intend to understand how B7-H3 protects RMS tumors from the immune system. Additionally, we will initiate the development of an antibody-based therapy that inhibits B7-H3 function and boosts anticancer immune response. This work will lay the foundation for the immediate clinical utility of developing clinical trials to assess the efficacy of B7-H3 blockade for the treatment of refractory and relapsed RMS.
These grants are made in addition to research grants to the University of Minnesota made in January of this year.
University of Minnesota Professor and medical oncologist Keith Skubitz has been treating people with sarcoma cancer for over 20 years. Maybe, he is your doctor. What he really seems passionate about is finding ways for science to help doctors deliver better treatments to their patients. This can mean anything from more effective drugs to portable pumps, which allow patients to take their chemo home.
Dr. Skubitz received his medical degree from the Johns Hopkins University, then completed his Internal Medicine training at the University of Minnesota. He took a fellowship in Clinical Pharmacology at Johns Hopkins and returned to Minnesota for his fellowship in Medical Oncology. Here he has stayed. Since 1988, Dr. Skubitz has led the University of Minnesota’s medical oncology treatment efforts for adult sarcoma patients.
Better Patient Care
One of the first things he did was to study the possibility that chemotherapy could be delivered differently. Drugs like ifosfamide had been given to patients in one or two big infusions, over several hours in the clinic. Dr. Skubitz thought it made more sense to deliver the drug slowly, over many days, by a continuous drip. He said “you knew from high school chemistry” that this might make the drug more effective. For one thing, the long steady drip could increase the chances the drug would be there in the body, active and available to hit new cancer cells as they were turned out by the tumor, day after day. This also could lessen side effects, because people would not need to absorb so much of the drug at once.
In about 1980, new technology made this option possible. Portable pumps could deliver a slow continuous drip to patients, even while they moved around freely or stayed at home, carrying their pumps in little packs. With a colleague, Dr. Skubitz studied this method and found that it worked. They published their findings, and many other doctors have followed the same approach.
Finding Better Medicines
Dr. Skubitz says his work is “certainly very interesting,” and sometimes he and his colleagues have “very satisfying results.” It is hard, however, that the treatments don’t always work. For many patients, “eventually, they stop working.” This is a “high stress” time.
One way to improve the situation is to find better medicines. Of course, this could mean making something totally new. But it also could mean making a new match, between an existing drug and an aggressive disease. University researchers have been part of just such a solution for giant cell tumors of the bone. These tumors usually do not kill people, but they can grow aggressively and there have not been good treatment options. Doctors use surgery and radiation when possible, but good results can be hard to get and even then, the tumors often grow back. It appeared to Dr. Skubitz and his colleagues that an antibody developed for osteoporosis might target these bone tumors. A small initial study showed that the drug did help. The University now participates in a world-wide follow-up study to consider the best dose and length of time to use the drug, which is seen as a very promising treatment.
Along the way, doctors also learned more about how tumor cells “talk” to normal cells. In this disease, tumor cells make a protein that recruits normal cells to come nearby and make something – call it factor x – that the tumor itself needs to thrive and grow. The drug works by blocking this protein, interfering with the tumor’s call for normal cells. With fewer normal cells stopping by to donate factor x, the tumor can’t grow so well anymore. Sometimes, it even dies.
Using New Science
Cutting-edge science clearly motivates Dr. Skubitz. On the list of scientific articles he’s written, there are many about genes. Dr. Skubitz tries to understand what tumors are telling us through the unique collection of genetic mutations and expressions they contain. When asked if the study of genetics will turn out to be an important thing for patients, Dr. Skubitz did not hesitate. “Absolutely,” it will.
Of course, genetic work could help doctors develop more effective treatments, targeted directly at the mistakes or pathways that allow the cancer to grow and spread. Even without a cure, genetic work could help doctors predict how dangerous a cancer will be. “Absolutely, definitely” it matters to know which cancers are most likely to be dangerous. This will affect the choices doctors make about treatment. Patients with less dangerous tumors could be spared the more intensive treatments; patients facing tougher battles could receive the most aggressive options.
Just this month, Dr. Skubitz was at a national cancer conference presenting results from a study that uses genes to help doctors separate the more aggressive cancers from the less dangerous ones. This work grew from one of RIS’ first seed grants. Years ago, University researchers including Keith Skubitz and his wife Dr. Amy Skubitz received a grant to identify the genetic signatures that might help doctors predict what cancers would do. The University’s tissue bank and the RIS grant allowed them to begin. Eventually, they found gene sets that appeared to break sarcoma cancers, ovarian cancers and kidney cancers into two main groups. They did not have enough information about what happened to the patients, though, to allow them to test the idea that the two tumor groups acted differently in people. Recently, the Skubitzes collaborated with researchers in Sweden and Denmark, who did have access to good follow-up information about patients. This work confirmed the sense that different gene sets appear in tumors that are more aggressive than in those less likely to be dangerous.
Another RIS-funded project that Dr. Skubitz works with is the clinical trial designed to test whether PET scans can show us which tumors are responding to chemotherapy. This is “quite neat,” because it may suggest better measures to test drug response. Using traditional methods, it could look like “you killed it off really well,” but then sometimes the tumor comes back. Doctors believe this may be due to the survival of a select group of deadly cells, sometimes called “cancer stem cells,” which may be great at hiding from toxic drugs or blocking their effects. If doctors could tell early on which tumors are being affected by a drug, they could spare patients who are not responding by stopping the drug and could switch them sooner to a potentially more effective option.
Always Surprising
When I asked Dr. Skubitz if there was anything else he thought we should know, he said this sounded an awful lot like the “classic internal medicine question.” Do your visits end with this invitation? Apparently, from the other side of the table, it is “striking” what patients will mention in closing. The doctor may have covered four or five major problems, and “you may think you know why they’re there,” but what’s really of concern to the patient may be something that’s “not even on your radar screen.” It’s surprising what you hear.
Hopefully, most of us can be thankful that our physicians do ask us for our concerns, and will listen for the surprise.
