Targeting the immunosuppressive effects of Myc-hyperactivation in high-risk osteosarcoma
Osteosarcoma (OS) is the most common bone tumor in the pediatric population. It is known for its aggressive nature and high tendency to spread to other parts of the body. Despite significant advancements in cancer treatment, effective targeted therapies for OS are still elusive. Notably, the MYC gene, commonly disrupted in various human tumors, including pediatric OS, is highly expressed in 20-30% of OS cases, accelerating tumor growth and spread. Our research aims to elucidate how MYC influences OS tumor growth and spread. To achieve this, we have recently developed a sophisticated animal model of OS by introducing Myc alterations in laboratory mice. Utilizing our Myc mouse model, we observe rapid tumor growth and spread compared to low-Myc OS models. Initial findings highlight Myc's dual role in promoting tumor growth and disrupting the surrounding non-tumor cells, notably impacting immune cell function, including macrophage function and antigen presentation, which are vital for the patient’s immune cell’s ability to recognize and kill the cancer cells. Our study aims to elucidate how MYC impairs the immune system's ability to identify and eliminate cancer cells, with the aim of pinpointing new treatment avenues for this highly aggressive population of OS tumors. By leveraging our preclinical findings and translating them into clinical applications, we aim to improve the quality of life and long-term survival rates for individuals facing this aggressive cancer.
Project Goal:
In our study, we are focusing on osteosarcoma (OS), a common and aggressive bone tumor that affects children and teens. Unfortunately, there is no effective targeted therapy currently available for OS. However, many OS patients have specific gene alterations, such as MYC, which is altered in 20-30% of patients and is associated with an extremely poor prognosis. Our goal is to understand how Myc affects both internal and external tumor features. Our early findings suggest that Myc does not just make the tumor grow faster, but also inhibits the ability of the patient’s immune system to fight cancer. First, we are looking into how MYC affects immune cell functions in OS. By studying altered MYC in mouse and human OS tumors, we hope to find new ways to improve the immune system’s ability to target tumors. Second, we are trying to understand how Myc stops the immune system from recognizing and attacking the cancer cells. By studying the genes involved in this process, we hope to find ways to boost the immune response against the tumor. We have found a promising lead with a drug called TAK-981, which showed enhancement in the immune response against Myc-driven OS. By understanding the role of Myc in suppressing the patient’s immune system and ability to eliminate the cancer, our goal is to develop new treatments specifically for this very high-risk population. Ultimately, we want to improve the chances of survival and quality of life for people with this aggressive OS.
