Grant: PJT PA: ICR - Lev. AI to Transform Can. Res. AI to Accelerate Cancer Research

Most cancer deaths are caused not by the original tumor, but by metastasis, when cancer spreads to distant organs such as bone, lung, liver, or brain. Different cancers tend to spread to different organs, and this often influences how aggressive the disease becomes. This pattern, known as metastatic organotropism, is well recognized but poorly understood. As a result, it remains difficult to predict or prevent metastatic disease. The goal of this project is to understand why cancer cells grow in some organs but not others. We will first analyze large collections of genetic and gene expression data from patients with metastatic cancer, including breast and prostate cancer. These analyses will identify molecular patterns linked to cancer spread to specific organs across multiple cancer types. We will then study these patterns in more detail using single-cell and spatial profiling data. This will allow us to determine which cancer cell populations express these programs, how they interact with surrounding tissues, and whether these features are already present in primary tumors or arise later during metastasis. Finally, we will test the function of key genes and pathways using gene-editing approaches in mouse models of prostate cancer. By turning selected genes on or off, we will determine which molecular programs are required for cancer cells to grow in specific organs. By combining large-scale data analysis with detailed cellular studies and functional testing, this project will improve our understanding of how metastasis develops. The findings may help identify biological markers that predict where cancer is likely to spread and uncover new treatment targets to limit or prevent the spread of cancer, ultimately improving patient outcomes.