Tumor exhibits altered metabolism, some of which is associated with radiation resistance. Recent work from our laboratory and others has demonstrated that radiation effectively modifies the microenvironmental metabolism, subsequently influencing DNA damage repair responses. Currently, there is a lack of strategies for targeting metabolism to sensitize tumors to radiation or protect normal tissue from its damage. This challenge partly arises from the complexity of cellular metabolism and the fact that existing work conducted in culture dishes may not accurately reflect the intricate microenvironment. Through CRISPR screens utilizing a comprehensive metabolic library in vitro and in vivo, we have identified pathways crucial for radiation sensitivity and resistance in non-small cell lung cancer. Our ongoing efforts are focused on validating these targets, understanding the underlying mechanisms, and developing metabolic tumor sensitizers and normal tissue protectors for clinical testing.
Potential impact
We anticipate this work will positively impact the lives of cancer patients undergoing radiation treatment and help safeguard national defense and the public from occupational and environmental exposure to radiation.
Techniques
In vivo and in vitro CRISPR screening, metabolomics, isotope-labeled nutrient tracing, biochemistry (western, IP, protein purification), molecular cloning, and radiobiological assays pertaining DNA damage and cell cycle.