Researchers at Georgetown University Medical Center and their colleagues have identified a biological pathway that is activated when tissue is starved of oxygen due to a rapid growth of a tumor, thus permitting cancer cells to make genetic changes so they can metastasize to the bone and thrive even when exposed to chemotherapy.
The path identified involves a receptor on the surface of a cancer cell, Y5R, that plays a role in controlling oxygen-deprivation effects if the cell was blocked or turned off, genetic changes would be limited, thus inhibiting 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. Near half of all Ewing sarcoma diagnoses are in people between the ages of 10 and 20, but almost all cases of Ewing sarcoma have occurred in white and Hispanic people. If the tumor spreads to distant areas at the time of diagnosis, survival rate is 38%, but it''s spread to between 8 and 14 percent.
Although the role of rapid genetic modifications in causing cancer growth is well known, the mechanisms which have been initiated are not well understood, and strategies to avoid them are lacking, according to Joanna Kitlinska, an associate professor at Georgetown University. That''s why our research focuses on the Y5Rs'' involvement in initiating such genetic modifications, as it gives us a target to aim at or block that might reduce cancer genome evolution and resulting progression to metastatic tumors that are resistant to chemotherapy.
Systemic cell-killing chemotherapy is needed to treat all cells in the body, leading to side effects. There are no therapies for genetic modifications that are used in routine treatment of Ewing sarcoma, which may increase the dose dose. In particular, adequate treatments for metastatic patients are lacking.
There are currently a number of therapeutics available that target Y5R because they are also linked to regulating food intake and psychiatric disorders. Several of these drugs have been successfully used in animal trials for obesity, but one of them was previously used in human clinical trials for obesity. However, most of them are designed to reduce functions in the brain that prevent food intake. These effects are not beneficial to cancer patients.
According to Kitlinska, we will keep conducting experiments in mice in order to establish what mechanisms are triggering Ewing''s spread to the bone. Ewing sarcoma may be beneficial to other cancer types that have high expression levels of Y5R, including another pediatric cancer, neuroblastoma, as well as common adulthood malignancies.