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Stories of progress, inspiration, and information in overcoming osteosarcoma.

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Breaking New Ground: The OSI’s 2024 Research Grant Recipients

Optimism surrounds osteosarcoma research as the OSI awards $1.1 million in cancer research funding to three innovative projects.

This year, the Osteosarcoma Institute (OSI) awarded $1.1 million in osteosarcoma research funding to three groundbreaking projects during its 2023–2024 grant cycle. After an extensive review process, the OSI’s committee of experts selected two translational studies and one high-risk, high-impact study.

Understanding Translational vs. High-Risk, High-Impact Cancer Research

Beginning in 2019, the OSI began awarding cancer research grants in three categories: translational research, clinical trials, and correlative science.

This year, under the guidance of Lee Helman, MD, an osteosarcoma expert who has been studying the biology and caring for pediatric patients with sarcomas for over thirty years, the OSI added a new, fourth category: high-risk/high-impact research.

Lee Helman, MD, Institute Director

“Current therapy for patients with osteosarcoma has not improved over the past 40 years. I believe that with our improved understanding of the genetic drivers of this disease, we have an unprecedented opportunity to make significant progress in treating patients using this information,” Dr. Helman says. “I also believe we have the opportunity to engage the immune system to help us develop new approaches for treatment. And I believe the OSI can help accelerate our progress in making this a reality.”

Translational research, often referred to as pre-clinical research, is aimed at bridging the gap between laboratory findings and clinical application. These studies are designed to uncover new biological insights that can lead to clinical trials and eventually improve patient outcomes.

“Translational studies are focused on identifying new information that could lead eventually to new clinical trials,” says Dr. Helman, who began his career at the National Cancer Institute (NCI), where he completed his fellowship and postdoctoral training in the Molecular Genetics Section in the Pediatric Oncology Branch. He served as Chief of the Pediatric Oncology Branch from 1997-2007 and as Scientific Director for Clinical Research in the Center for Cancer Research, National Cancer Institute from 2007 to 2016.

In contrast, high-risk/high-impact research supports bold, pioneering ideas that challenge traditional approaches. These projects may not have extensive preliminary data but possess the potential to make a significant breakthrough in the field.

“The idea behind this is that doing the same old thing hasn’t made a big difference,” says Dr. Helman, who continues his work today as Director of the Osteosarcoma Institute and as an adjunct professor at Children’s Hospital Los Angeles. “We’re really struggling with making some breakthroughs in treating our patients with osteosarcoma.”

By funding these innovative studies, the OSI aims to catalyze the development of transformative therapies that can reshape osteosarcoma treatment.

2024 Osteosarcoma Research Grant Recipients

Out of more than 30 applicants, the OSI selected the following grant recipients. These projects aim to deepen our understanding of osteosarcoma and develop new treatments for this challenging cancer.

“The outcome we are looking for is to have more patients survive osteosarcoma,” Dr. Helman says. “I think each of these grants has a very good chance of getting answers to some important questions that we can then build on to make that happen.”

Exploring the Pre-Metastatic Niche and Pulmonary Metastasis Prevention

Principal investigator: David C. Lyden, MD, PhD, Weill Cornell Medicine
Project title: Targeting the Axis of Tumor-Derived Extracellular Vesicles, Lung Macrophages, and Neutrophil Extracellular Traps to Prevent Pulmonary Metastasis in Osteosarcoma
Funding awarded: $500,000

David Lyden, MD, PhD

Dr. Lyden’s project focuses on understanding how tumor-derived extracellular vesicles (EVs) contribute to the formation of the pre-metastatic niche in the lungs — a key site for osteosarcoma metastasis. These vesicles, which carry molecules from the tumor to distant sites, play a crucial role in conditioning the lungs to become receptive to tumor growth.

By identifying and targeting specific components within these EVs, such as cytokines and integrins, Dr. Lyden’s team aims to disrupt the establishment of metastatic sites and prevent the spread of osteosarcoma. This research holds the potential to uncover new therapeutic targets that could prevent metastasis to the lungs, a common and deadly progression in osteosarcoma patients.

“The outcome we are looking for is to have more patients survive osteosarcoma,” Dr. Helman says. “I think each of these grants has a very good chance of getting answers to some important questions that we can then build on to make that happen.”

Enhancing CAR-T Therapy with Modified NK Cells

Principal investigator: Robin Parihar, MD, PhD, Baylor College of Medicine
Project title: Modified NK Cells to Decrease Toxicity and Enhance Efficacy of GD2.CAR-T Cells for Treatment of Osteosarcoma
Funding awarded: $500,000

Robin Parihar, MD, PhD

Dr. Parihar’s study seeks to improve the efficacy of CAR-T cell therapy for osteosarcoma by modifying natural killer (NK) cells. CAR-T therapy, though promising in blood cancers, has faced challenges in solid tumors like osteosarcoma due to the immunosuppressive environment surrounding the cancer cells.

This innovative approach involves engineering NK cells to alter this environment, making it more favorable for CAR-T cells to function. By reducing the toxicity commonly associated with CAR-T therapies and enhancing their effectiveness, this research could pave the way for more successful immunotherapy options for osteosarcoma patients.

Importantly, since our award was made, Baylor and Dr. Parihar have received a substantial $4.5M Cancer Prevention and Research Institute of Texas grant, part of which is dedicated to building on the foundation laid by our grant and advancing this technology into a planned clinical trial in osteosarcoma and neuroblastoma.

Targeting DNA Structures to Block Metastasis

Principal investigator: Poul Sorensen, MD, PhD, BC Cancer, part of the Provincial Health Services Authority
Project title: G-quadruplex Binders as a Promising Therapeutic Strategy in Metastatic Osteosarcoma
Funding awarded: $100,000

Poul Sorensen, MD, PhD

Last year, thanks to the support of the Hartz and Alwan families, Dr. Sorenson was awarded a $500,000 grant to study immunotherapy. Building on the success of that ongoing study, which came to fruition through the OSI’s Partnering for Progress program, Dr. Sorensen’s new high-risk/high-impact study explores a novel approach to osteosarcoma treatment by targeting G-quadruplex structures within cancer cells. These unique DNA and RNA formations influence gene expression and DNA repair, playing a critical role in cancer cell survival and metastasis.

Dr. Sorensen hypothesizes that stabilizing these structures using G-quadruplex binders could induce high levels of DNA damage in osteosarcoma cells, particularly those metastasizing to the lungs resulting in death of these cells. By preventing the establishment of lung metastases, this innovative strategy could lead to new therapies that address one of the most challenging aspects of osteosarcoma.

Pushing the Boundaries of Osteosarcoma Research

The OSI’s commitment to fund intrepid research reflects our mission to drive advancements in osteosarcoma treatment. As we continue to support pioneering research, these projects exemplify the drive to uncover new insights and develop transformative treatments for osteosarcoma patients.

Stay tuned for updates on these exciting studies as they progress toward changing the landscape of osteosarcoma care.

If you are interested in co-funding research with the OSI, please email giving@osinst.org.

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