Researchers from Georgetown University Medical Center and their colleagues have identified a biological path that is activated when tissue is starved of oxygen due to a rapid growth of a tumor, thereby allowing cancer cells to make genetic changes so they can meetastasize to the bone and thrive even when exposed to chemotherapy.
The pathway identified involves a receptor on the surface of a cancer cell, called Y5R, which plays a role in meditating oxygen-deprivation effects if it was blocked or turned off, genetic modifications would be limited, thus inhibiting metastasis of a tumor.
InNature Communications, the findings were published on April 28, 2022.
Every year, about 200 children and young adults in the United States are diagnosed with an Ewing tumor. Nearly half of all Ewing sarcoma diagnoses are in people between the ages of 10 and 20, but there are usually white and Hispanic people with the tumor. If the tumor spreads to distant areas at the time of diagnosis, survival rate is 8 to 14.9%.
While the utility of rapid genetic changes in the growth of cancer is well known, the mechanisms that are initiating these changes aren''t well understood, and strategies to mitigate them are lacking, according to Joanna Kitlinska, the researcher at Georgetown University. This is why our identification of Y5Rs'' involvement in the development of such genetic modifications is crucial, as it allows us to a target to target or block, that might lead to tumor growth and subsequent path to metastatic tumors.
Systemic cell-killing chemotherapy is required to treat all cells in the body, leading to side effects. There are no therapies that are used in routine treatment of Ewing sarcoma, which may reduce symptoms. In particular, adequate therapies for metastatic patients are lacking.
There are currently a number of drugs available that target Y5R because they are also linked to regulating food intake and psychiatric illnesses. Several Y5R-targeted medications have been successful in animal studies; one of them was found in human clinical trials for obesity. However, the main challenge will be to develop Y5R-targeted drugs that do not cross the blood-brain barrier, because these effects are undesirable in cancer patients.
According to Kitlinska, we will continue performing experiments in mice in order to help to identify the mechanisms that triggered the spread of Ewing to the bone. Ewing sarcoma may be helpful for other cancer types known to have high expression levels of Y5R, including another pediatric cancer, neuroblastoma, and common adulthood malignancies.