Osteosarcoma researcher Jason T. Yustein, MD, PhD, seeks to better understand the disease by testing various combinations of drugs to treat it.
Immunotherapy has been one of the most promising areas of cancer research in the past few decades. It is now approved to treat many types of cancers, including breast cancer, leukemia, liver cancer and others. But immunotherapy has not been successful in treating some cancers, and unfortunately, that includes osteosarcoma.
“Thus far, immune-based therapeutic approaches for sarcomas have not been extremely successful,” says osteosarcoma researcher Jason T. Yustein, MD, PhD, of Emory University’s Winship Cancer Institute. “But there is a lot of research going on in this field, and a lot of us are trying to make progress and improve how we can help the patients’ own immune systems fight the disease.”
Dr. Yustein’s osteosarcoma treatment research, made possible through a 2022 Osteosarcoma Institute grant, currently focuses on combining immunotherapy with targeted therapy. The OSI grant is funded by contributions from the Scott Shockley Foundation and the Rally Foundation for Childhood Cancer Research.
Exploring Checkpoint Inhibitors
Researchers can engineer immunotherapies to work in different ways. Some immunotherapies are what scientists call checkpoint inhibitors. These drugs help the immune system recognize and attack cancer cells.
Jason T. Yustein, MD, PhD
“A lot of tumor cells will express certain proteins on their surface to disguise themselves against the patient’s immune system,” says Dr. Yustein, also the Director of Solid Tumor Translational Research at the Aflac Cancer and Blood Disorders Center of Children’s Healthcare of Atlanta. “These proteins, called checkpoints, keep the patient’s immune cells from recognizing the tumor cells and destroying them.”
Checkpoint inhibitors work by essentially deactivating these proteins so the patient’s immune cells can identify the tumor cells and attack them. They are effective at treating several types of solid tumors, including lung cancer and melanoma.
“Checkpoint inhibitors have improved patient outcomes in certain diseases quite a bit,” Dr. Yustein says. “For the most part, though, there have not been many significant responses in osteosarcoma, at least not when these types of inhibitors are used alone.”
Better Together?
Just because immunotherapy has not been particularly effective at treating osteosarcoma does not mean it lacks potential. Dr. Yustein’s lab is currently exploring ways that immunotherapy could be successful by learning how the environment around osteosarcoma tumors can influence treatment success.
“For this particular project for the Osteosarcoma Institute, we are specifically working on improving some of these immunotherapeutic approaches,” Dr. Yustein says. “How can we enhance the efficacy of immune checkpoint inhibitors?”
Dr. Yustein says he thinks the answers could lie in combination immunotherapy.
“We are examining combining targeted therapy that can have dual effects by directly targeting the sarcoma cell and also changing the tumor microenvironment. Changing the microenvironment would allow greater infiltration of immune cells that can destroy the osteosarcoma cells more effectively when combined with immune checkpoint inhibitors,” Dr. Yustein says.
Progress in Treatment Research for Osteosarcoma
In addition to studying checkpoint inhibitors, Dr. Yustein’s lab has been instrumental in developing diverse osteosarcoma mouse models in which to test different therapies. Dr. Yustein’s lab shares these models with labs around the world to make it easier for other researchers to test their therapies. The models also offer insight into the disease itself.
“I think we are getting to a point where we will start pushing the needle forward on these more high-risk states, particularly the metastatic disease, the relapses, and the treatment-resistant diseases.” — Jason T. Yustein, MD, PhD
Terriann Shockley and Jason Yustein, MD, PhD. Dr. Yustein is the recipient of an Osteosarcoma Institute grant funded by contributions from the Scott Shockley Foundation and the Rally Foundation.
“Our research team has created special mouse models that closely resemble human osteosarcoma, allowing us to study how these cancers grow and respond to new treatments,” Dr. Yustein says. “We have also made cell lines from these mouse tumors that can be put into healthy mice, which allows us to test how well different treatments work in a controlled environment.”
With each project, Dr. Yustein and other researchers gain a better understanding of osteosarcoma and what makes it so difficult to treat. So even when hypotheses do not pan out, Dr. Yustein does not consider it a failure.
“There are some fantastic people out there working to understand and develop new therapies for osteosarcoma,” he says. “I think we are getting to a point where we will start pushing the needle forward on these more high-risk states, particularly the metastatic disease, the relapses, and the treatment-resistant diseases.”
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