Researchers from the Georgetown University Medical Center and colleagues have identified a biological pathway that is activated when tissue is starved of oxygen due to rapid growth of a tumor, thus permitting cancer cells to make genetic modifications so they can meetastasize to the bone and thrive even when exposed to chemotherapy.
Y5R, a receptor on the surface of a cancer cell, is used to determine oxygen-deprivation effects, which might be limited by blocking or turning off genetic changes, thereby preventing metastasis of a tumor.
InNature Communications, the finding was published on April 28, 2022.
Every year, about 200 children and young adults in the United States are diagnosed with an Ewing tumor. About half of all Ewing sarcoma diagnoses are in people between the ages of 10 and 20, and almost all cases of Ewing sarcoma are found in white and Hispanic people. The 5-year survival rate is 38 percent, but if the tumor spreads to the bone, survival drops to 8 and 14 percent.
Although the role of rapid genetic mutations in boosting cancer development is well known, the mechanisms that are leading these changes are inadequate, and strategies to protect them are lacking, according to Joanna Kitlinska, a PhD. In this context, our recognition of Y5Rs'' involvement in the formation of such genetic modifications is vital, as it gives us a target to pursue or block that might prevent cancer genome evolution and the progression of metastatic tumors.
Systemic cell-killing chemotherapy, which can affect all cells in the body, leads to side effects. There are no treatments to genetic changes that are used in routine treatment of Ewing sarcoma, which might reduce dosage symptoms. In particular, adequate therapies for metastatic patients are lacking.
There are currently a number of medications that target Y5R because they are also involved in regulating food intake and psychiatric disorders. Several Y5R-targeted drugs have been successfully used in animal studies, but one of them was used in human clinical trials for obesity. However, most of them are designed to bypass functions in the brain that inhibit food intake. These effects are not beneficial to cancer patients.
According to Kitlinska, we will continue conducting experiments in mice in order to determine the mechanisms causing the spread of Ewing to the bone. Ewing sarcoma may be beneficial for other cancer types known to have excellent expression levels of Y5R, including another pediatric cancer, neuroblastoma, as well as common adulthood malignancies.