A Ludwig Cancer Research study has uncovered a key mechanism by which tumors develop resistance to radiation therapy and shown how such resistance might be overcome with drugs that are currently under development. The discovery addresses a longstanding challenge: as many as 40% of large tumors develop resistance to radiotherapy, significantly complicating treatment. Overcoming such resistance could go a long way toward treating tumors, especially those that cause significant discomfort to patients and resist other modes of therapy or cannot be surgically removed.
A Ludwig Cancer Research study has uncovered a key mechanism by which tumors develop resistance to radiation therapy and shown how such resistance might be overcome with drugs that are currently under development. The discovery addresses a longstanding challenge: as many as 40% of large tumors develop resistance to radiotherapy, significantly complicating treatment. Overcoming such resistance could go a long way toward treating tumors, especially those that cause significant discomfort to patients and resist other modes of therapy or cannot be surgically removed.
“It has been known for some time that radiation induces inflammation, and we’ve shown in our earlier work that it does so through a molecular sensor found in cells known as the stimulator of interferon genes, or STING,” says Ralph Weichselbaum, co-director of the Ludwig Center at Chicago, who led the study with Yang-Xin Fu of the UT Southwestern Medical Center. “However, there’s a dark side to radiation: after it causes good inflammation—which mounts an immune attack on cancer cells in the irradiated tumor—it causes a bad kind of inflammation that suppresses immune responses.”
STING detects DNA fragments inside cells, fragments generated by the damage high energy radiation does to chromosomes. In previous studies, Weichselbaum, Fu and their colleagues showed that STING links the detection of such fragments to the production of immune factors known as type 1 interferons. These factors ultimately boost the activation of killer T cells—immune cells that attack sick and cancerous cells—and cause much of the destruction of tumors associated with radiation therapy.
Read more at Ludwig Institute for Cancer Research
Image: Ralph Weichselbaum is the co-director of the Ludwig Center at Chicago. (Credit: Ludwig Cancer Research)
