Kristen VanHeyst, DO

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University Hospitals Rainbow Babies & Children’s Hospital (Cleveland, OH)

CureSearch Young Investigator Award: 2023-2025 

Focus: Pediatric Osteosarcoma; Tumor Microenvironment; Immunotherapy

Project title: Tumor Microenvironment Modulation as an Effective Therapy for Osteosarcoma

Kristen VanHeyst, DO

Osteosarcoma is the most prevalent aggressive primary malignancy of the bone affecting children and young adults. Although overall survival in patients with osteosarcoma has improved with advances in therapy, there have been no significant improvements in survival outcomes in patients with metastatic pulmonary osteosarcoma. Due to the complex genetic heterogeneity of osteosarcoma, molecular-targeted therapy approaches are not feasible. For this reason, novel therapeutic approaches are desperately needed.

Kristen VanHeyst, DO, from Rainbow Babies and Children's Hospital, is working to establish the efficacy of a novel TGF-beta I receptor inhibitor for the treatment of osteosarcoma. The presence of TGFß contributes to making the tumor microenvironment more hospitable to tumor cells and dampens the ability of the patient's own immune system to eradicate this tumor. This project is a novel possibility that may highly impact the survival of pediatric and adolescent/young adult patients with metastatic pulmonary osteosarcoma or refractory osteosarcoma by offering real clinical opportunities for treatment.

Research Update April 2024: 

Osteosarcoma is the most common aggressive bone cancer that affects children and young adults. At the time of diagnosis, some patients have osteosarcoma not only in their bone, but also in their lung(s). Osteosarcoma is typically treated with a combination of surgical resection and chemotherapy. Despite this treatment, the prognosis for patients with osteosarcoma in both their bone and lung(s), or who have the disease that does not respond to this treatment or recurs, is very poor. Treatment of patients with metastatic, progressive or relapsed disease, therefore, remains a significant challenge and novel therapeutic approaches are desperately needed. 

Transforming Growth Factor Beta (TGF-beta) is produced by osteosarcoma cells and cells that exist within the tumor’s environment. The presence of TGF-beta makes it more difficult for a patient’s own immune system to eradicate this tumor. Dr. VanHeyst’s prior data supports the use of an inhibitor of TGF-beta as a therapeutic option for patients with recurrent/refractory osteosarcoma and led to the developmental of a clinical trial using a TGF-beta inhibitor. 

Dr. VanHeyst and her team want to further examine the effects of this TGF-beta inhibitor on the environment in which osteosarcoma cells live in addition to combining it with other forms of therapy that stimulate the patient's immune system to fight the osteosarcoma. They are actively working toward these goals and plan to repeat their most recent experiments with modifications to strengthen the validity of the results they obtained. The outcome of this project may improve therapeutic options and potential survival for children, adolescents and young adults with osteosarcoma. 

"This project will expand upon our current trial design. We aim to ultimately lower the age limit for enrollment onto the trial, which will allow more pediatric patients access to novel therapeutic options.”
- Kristen VanHeyst, DO

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