by Researchers have made a significant breakthrough in the understanding of how breast cancer cells evade detection by the immune system. A pathway known as cGAS-STING, responsible for activating the immune response against DNA damage, has been found to play a crucial role in preventing the formation of cancer cells. This discovery could pave the way for developing new treatments and prevention strategies for breast cancer.
The study, led by Gaorav Gupta, MD, Ph.D., associate professor in the Department of Radiation Oncology at the UNC School of Medicine, revealed how the cGAS-STING pathway is activated to detect DNA damage within cells. This pathway is normally turned off to prevent excessive inflammation in healthy conditions. However, breast cancer cells seem to have lost this pathway, allowing them to withstand high levels of DNA damage without being recognized by the immune system.
The key to unlocking the cGAS-STING pathway lies in an enzyme called cyclic GMP-AMP synthase (cGAS), which acts as a messenger for the immune system. When cells are damaged, cGAS detects the threat and signals the immune system to eliminate it from the body. Previous research had shown that cGAS is normally locked up and unable to recognize DNA unless it is freed by a specific trigger.
Researchers at the UNC Eshelman School of Pharmacy and the Department of Biochemistry and Biophysics had previously discovered that a protein called MRE11 recognizes broken fragments of DNA. In the recent study, the team found that MRE11 not only recognizes DNA damage but also releases cGAS from its inactive state by binding to broken DNA. This activates the immune response against cancer cells and helps eliminate them before they develop into tumors.
Furthermore, the study found that the interaction between MRE11 and cGAS triggers a specialized form of cell death, called necroptosis, which activates the immune system. Necroptosis leads to the death of cells in a manner that promotes immune activation, making it easier for the body to fight against cancer cells.
The researchers believe that linking MRE11 and cGAS to necroptosis activation can effectively suppress tumor formation. By activating an immune-boosting form of cell death, damaged precancerous cells can be eliminated, preventing the development of cancer.
Based on these findings, Gaorav Gupta and his colleagues are conducting a clinical trial at the UNC Lineberger Comprehensive Cancer Center to investigate the combination of radiation and immunotherapy for the treatment of certain types of breast cancer. The researchers aim to determine if these therapies can effectively engage the cGAS-STING pathway and improve clinical outcomes.
In conclusion, the discovery of the key that unlocks the cGAS-STING pathway and activates the immune response against breast cancer cells is a significant step forward in cancer research. It provides insights into potential strategies for preventing and treating breast cancer and opens up new possibilities for targeted therapies that can boost the immune system’s ability to eliminate cancer cells. Further studies and clinical trials will help validate these findings and explore their application in clinical practice.
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1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it
