Scientists have uncovered how a rare and aggressive kidney cancer, translocation renal cell carcinoma (tRCC), develops. This cancer, mainly affecting children and young adults, is caused by abnormal hybrid genes called TFE3 oncofusions. These genes hijack the cell’s machinery to form liquid-like structures, or “droplet hubs,” inside the nucleus.
RNA, instead of only carrying genetic messages, acts as a structural builder for these droplets. The droplets then serve as command centers that activate growth-related genes, speeding up tumor development. An RNA-binding protein called PSPC1 stabilizes these droplets, making them strong cancer drivers.
Using advanced tools such as CRISPR and proteomics, the researchers created a nanobody-based chemogenetic switch that attaches to the cancer-driving fusion proteins. When triggered, it dissolves the droplets and stops tumor growth. This discovery halted cancer in lab and mouse models and could lead to a new, precise, and less toxic therapy for tRCC and other pediatric cancers caused by similar genetic fusions