New research has identified potential therapeutic targets and developed a unique delivery system to treat osteosarcoma, a bone cancer that primarily affects children and adolescents.
The standard treatment plan for osteosarcoma today is no different from when it was first introduced nearly 50 years ago. However, nearly a third of patients relapse and require new interventions. This prompted Fiona Freeman, assistant professor, UCD School of Mechanical and Materials Engineering and Fellow, UCD Conway Institute, in Ireland, to focus on the possible therapeutic use of microRNAs in osteosarcoma, and specifically on a molecule called miR-29b.
MicroRNAs are a family of molecules that help control certain activities in cells such as growth and development. They show promising results in the treatment of cancer and viral infections. This study introduces for the first time, the therapeutic potential of miR-29b in inhibiting the growth of osteosarcoma tumors and the potential of nanoparticles as a vehicle for therapeutic delivery to treat cancer.
Suppress tumor growth
“The main findings of our study show that when administered locally via an injection delivery system, our miR-29b nanoparticle enhances the therapeutic potential of chemotherapy and suppresses tumor growth while aiding in repair of damaged surrounding bone even while patients are undergoing chemotherapy treatment,” said Freeman, who led the research.
The current gold standard treatment option requires extensive surgical and chemotherapy interventions leading to a poor prognosis and reduced quality of life. Due to the aggressive nature of the disease, surgical intervention usually involves complete reconstruction of the limb or in many cases amputation.
In addition, chemotherapy and osteosarcoma tumors have been shown to impair the ability of bone to repair after surgical intervention.
“Any bone regeneration strategy that will help regenerate damaged bone will greatly benefit these young patients so they don’t lose their limbs. However, there is a fine balance between trying to promote bone regeneration and promoting tumor growth, which has significantly slowed fundamental research and clinical translation of tissue engineering strategies for cancer patients.”
The team developed the miR-29b formulation: nanoparticles that are delivered via a hyaluronic acid-based hydrogel to allow localized and sustained release of the therapy.
Approach to removing osteosarcoma
“This work seeks to answer important basic science questions, such as the balance between inducing tissue regeneration and preventing tumor recurrence, and how gene therapy approaches can help eliminate osteosarcoma in combination with standard chemotherapy,” said Natalie Artzi, an associate professor at Brigham Women’s Hospital and Massachusetts Institute of Technology, which is the report’s senior author.
The hyaluronic based injection system turns into a gel on target areas of the body within minutes and allows local and continuous delivery of miR-29b to the primary tumor site. Doctors will be able to inject directly into the site of the defect during the tumor removal procedure, as no UV or temperature is required for gelation. Thus, this local therapy has the potential to be integrated into current clinical treatment regimes as an adjunct to conventional chemotherapy. This may further improve clinical outcomes for these young patients.
The research team also validated the therapeutic potential using two disease prediction models; 3D co-culture spheroid model; and an orthotopic metastatic murine model.
“Fiona’s findings have the potential to revolutionize cancer treatment and improve outcomes by providing important information that can inform the design of future combination therapies for these young patients,” said Daniel Kelly, professor of tissue engineering at Trinity College Dublin and principal investigator Amber, who co-authored the study. author of the report.
The importance of pulmonary metastases
On a potential next step for this research, Freeman said: “This innovative microRNA therapy could potentially be given to osteosarcoma patients soon after cancer diagnosis, prior to surgical intervention, to reduce tumor spread to other places in the body (metastasis), which is critical in patient survival. .
“Lung metastases are the most critical clinical factor. 70% of patients with pulmonary metastases die from the disease within three years. This therapy can significantly affect the overall survival rate of these young patients. The therapy can be applied locally, after surgery to remove residual malignant cells that can cause tumor recurrence while repairing bone damaged during chemotherapy, providing an important alternative to preventing limb amputation.”