Richard Lu, Ph.D., a professor in the UAB Department of Pediatrics and the lead principal investigator involved in the study. High-risk neuroblastoma is a pediatric cancer that develops in the nerve tissue and frequently spreads throughout the body. According to the American Cancer Society, it commonly occurs in children who are less than 1 year old. Neuroblastomas are the most common and deadly extracranial childhood tumors, accounting for 15 percent of all pediatric cancer deaths. Researchers at the University of Alabama at Birmingham O’Neal Cancer Center published a study in Science Advances exploring some of the underlying mechanisms of metastatic high-risk neuroblastomas and two potential drug targets that could target vulnerabilities found in this disease.
During this study, researchers examined how high-risk neuroblastoma compares to low-risk neuroblastoma, which does not spread throughout the body. They found that high-risk tumor cells are biologically different. These cells are more adaptive to and evade the body’s immune defenses. These cancer cells can be shielded within the lymph nodes from the body’s immune system. The lymph nodes provide an immune-suppressive microenvironment that weakens and exhausts T cells from attacking the cancer cells and defending the body. This allows the cancer cells to survive and continue spreading throughout the body.
Researchers found that these metastatic tumors have increased protein production and rely heavily on two biological pathways that help cancer cells efficiently make proteins and transport them to the right places inside the cell to support tumor growth and survival. When they used drugs to simultaneously block both pathways, they found that tumor growth slowed dramatically and survival improved in pre-clinical models.
“Think of cancer cells as a factory with both a production line and a delivery system,” said Richard Lu, Ph.D., a professor in the UAB Department of Pediatrics and the lead principal investigator involved in the study. “It produces large amounts of proteins and quickly delivers them to the places where they are needed to perform specific jobs, helping the cancer cells grow and survive. If we can reduce the production of these proteins while also disrupting their delivery within the cell, we may be able to slow tumor growth and make cancer cells more vulnerable to chemotherapy or immunotherapy.”
In the future, researchers plan to explore ways to change the tumor environment in the lymph nodes and use immunotherapy to block the signals that suppress the immune response. By making this environment more favorable for an immune response, Lu says, they hope to restore the ability of T cells to recognize and attack cancer cells that are shielded within the lymph nodes.
Each year, there are approximately 600 to 800 new cases of neuroblastoma in the United States, according to the ACS. Lu says metastatic tumors typically found in high-risk neuroblastoma are drug resistant and lethal to the patient. In the future, researchers hope to study whether combining approaches that modify the tumor environment with targeted chemotherapy and immunotherapy can more effectively treat this aggressive disease and improve outcomes for patients.