Karuna Ganesh, MD, PhD

Colorectal cancer is the second most common cause of cancer death. Immunotherapy is largely not effective in this disease. To work safely, it requires targets in tumors that are not also present in normal tissue. These are difficult to find. Our recent research shows that advanced colorectal cancers adopt a fetal-like state. This fetal-like state reactivates gene programs that are normally only expressed during early development. In normal adult tissues, these programs are turned off. This may make advanced cancer vulnerable. Reactivated fetal proteins could potentially be used as targets for new immunotherapies. Here we propose to study how these fetal proteins are recognized by the immune system. For this, we will use our unique and extensive biobank of organoids. Organoids are 3D cultures of cancer cells derived directly from patient tumors and normal cells. They are a more informative and realistic model of cancer than traditional cell cultures. We must first understand which molecules are shown to the immune system in cancer cells. We will then look for immune cells in the blood of colorectal cancer patients that can recognize the fetal molecules. This approach will ultimately lead to novel immunotherapies. These could help treat advanced colorectal cancer and related solid tumors.