An investigation of the engagement of cGAS-STING signaling upon DNA damage in cancer cells

When cancer cells undergo DNA damage, leakage of DNA to the cytoplasm can triggers an immune response which can be both anti-and pro-tumorigenic. This response relies on a pathway called the cGAS-STING pathway. Although this pathway is known to have anti-cancer properties, it can also produce pro-inflammatory and pro-tumorigenic factors that promote cancer growth. In this PhD project, we found that inhibiting the cGAS-STING pathway can reduce the production of pro-tumorigenic factors in some cancer cells. We also discovered that inhibiting downstream modulators of NF-κB signaling, such as ERK1/2, could help limit inflammation while retaining anti-proliferative effects. Additionally, we found that inhibiting the extracellular secretion of 2'3' cGAMP could also reduce inflammation. These findings suggest new strategies for improving cancer treatment.