Our Work

This study aims to overcome a key challenge in CAR-T immunotherapy for children with osteosarcoma: the inhibitory tumor microenvironment. Bone cancers have a unique environment that suppresses CAR-T cells and can produce toxicities like cytokine release syndrome (CRS). The study will test a strategy to enhance CAR-T effectiveness by administering specialized Natural Killer (NK) cells designed to eliminate the suppressive elements of the tumor microenvironment prior to T cell therapy. Dr. Parihar’s OSI study is generously supported by The Jordan Spieth Family Foundation, Fabulous Faith’s Foundation, Scott Shockley Foundation, and the Shumiestrong Osteosarcoma Science Fund at the OSI in memory of Faith Lautzenheiser, Scott Shockley, and Sam Shumadine.

This 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.

Dr. David Lyden is an authority on the mechanisms by which cancer metastasizes throughout the body, particularly through the establishment of blood vessels that feed the growth and spread of tumors. Dr. Lyden has found that tiny extracellular vesicles (EVs) released by osteosarcoma tumors travel to the lungs where they prepare pre-metastatic niches that promote osteosarcoma pulmonary metastases. Dr. Lyden’s interdisciplinary team is well positioned to address these complex biological processes.

The MYC protein, a transcription factor encoded by the MYC gene, plays a critical role in cell cycle regulation and oncogenesis. MYC amplification is a common feature of osteosarcoma and is associated with poor outcomes. It has long been regarded as undruggable but, in early 2024, the Spanish company Peptomyc reported promising results of a Phase 1 clinical study in solid tumors (Nature Medicine 30, 762-771). This phase 2 trial is sponsored by the OSI and supported in collaboration with Curing Kids Cancer, The Morgan Adams Foundation, and The Kristen Ann Carr Fund. It is a 10-patient open-label, single-center, single-arm Phase 2 pilot study to serve as a proof-of-concept of OMO-103 safety and activity in patients with advanced high-grade osteosarcoma.

This study is supported by the Miles of Hope Fund at the OSI in loving memory of Miles David Hartz and the Team Lydia Osteosarcoma Science Fund at the OSI in honor of Lydia Alwan. The study aims to identify new proteins that are unique to the surface of metastatic osteosarcoma cells and so can serve as immunotherapy targets. Once the team identifies possible targets, the next step will be to develop antibody-drug conjugates or CAR T cells that can selectively block those proteins and test whether the treatment is successful in reducing tumor growth.

This is one of two studies exploring the causes and effects of the profound genomic instability that is a hallmark of osteosarcoma. This project will develop novel experimental and computational methods to study these matters using clinical samples and a novel data analysis framework based on evolutionary biology not previously applied to study this disease. A major focus will be the identification of proteins involved in the generation of complex genome aberrations during the development of osteosarcoma with the aim of identifying novel targets amenable to targeted therapy or immunotherapy.

This second genomic study exploring the causes and effects of the profound genomic instability that is a hallmark of osteosarcoma will delineate the mutational processes and mechanisms by which pervasive chromosomal instability, including duplications or deletions of large segments of DNA, fuel osteosarcoma progression and immune evasion.

This study is a canine clinical trial that aims to increase the efficacy of chimeric antigen receptor (CAR) T cell therapy by supplementing the cellular immunotherapy with additional agents intended to modify the tumor microenvironment, making it more susceptible to CAR T cell therapy. Robust correlative science will track and quantify the impact of these combinations.

This study is supported by the OSI and The Scott Shockley Foundation in loving memory of Scott Shockley. The study will evaluate combining two approaches to osteosarcoma therapy that may work together synergistically: immunotherapy, which utilizes the immune system to attack cancer cells, and targeted therapy that specifically blocks signals that are needed for the growth of cancer cells. The studies will be conducted in mouse osteosarcoma tumors that are believed to closely resemble human osteosarcoma.

Commenced in July 2022, this study is supported by the OSI and Fabulous Faith’s Foundation in loving memory of Faith Rose Lautzenheiser. Shorthand for “stimulator of interferon genes,” STING is a feature of the immune system: a sensor that triggers an immune, cell-killing response. Dr. Sweet-Cordero’s research, using mouse models, aims to discover if something about osteosarcoma can be used to activate this pathway.

Commenced in July 2021, this laboratory study is supported by Lizzy’s Osteosarcoma Science Fund at the OSI in loving memory of Lizzy Wampler. It will evaluate whether, as an alternative to surgical biopsies, a sufficient number of tumor cells can be isolated from the blood draw of a patient being treated for osteosarcoma to enable analysis of their progress. If this proves feasible, doctors will be able to ascertain much earlier whether a treatment is working or a different treatment should be tried.

Commenced in July 2021, this study in dogs will assess whether utilizing cutting-edge techniques to enhance the efficiency of the body’s own immune system against osteosarcoma, in combination with radiation therapy, has the potential to be a safe and effective treatment for human osteosarcoma patients.

Commenced in January 2020, this study will evaluate the combination of two drugs that inhibit DNA repair pathways critical to the survival of osteosarcoma cells. This is the first study to test this combination in osteosarcoma patients.

Commenced August 2020, this laboratory study was supported by the Hartz Family Osteosarcoma Fund at the OSI in memory of Miles Hartz. This study evaluates new drugs called antibody drug conjugates, or ADCs, combining a drug payload linked to a targeted antibody that specifically delivers the anticancer drug to osteosarcoma cells. Antibody drug conjugates are a brand new, very promising technology. ADCs are a way to build drugs that has never been done before and have had amazing success in some cancers.

Commenced August 2020, this laboratory study evaluates the communication that must occur between osteosarcoma tumor cells and the normal lung to allow lung metastatic disease to occur. The hope is that understanding these communications could identify potential new drug targets to inhibit growth of lung metastases in osteosarcoma.

Commenced February 2020, this laboratory study evaluates the potential role of new mechanisms to inhibit a gene required for cells to proliferate, called CDK4, to block the ability of osteosarcoma to metastasize.

Commenced April 2019, this was the initial investment with Honor Health Research Institute to begin offering support and guidance through OSI Connect (formerly OSI Hotline) to osteosarcoma patients and their families free of charge. Through OSI Connect, an experienced, knowledgeable osteosarcoma physician will meet with you about all aspects of this terrible disease, including treatment, possible side effects, and advice for getting the most out of your visits with your treating physician.

Commenced December 2020, this study evaluates the combination of two drugs with unique mechanisms of action in an attempt to harness the immune system to attack osteosarcoma tumors in patients. This is the first use of this combination of drugs in osteosarcoma patients. The Rally Foundation for Childhood Cancer Research partnered with the Osteosarcoma Institute to co-fund this study.