## New Research Offers Potential “Switch” to Halt Aggressive Childhood Cancer
A team of researchers has identified a critical mechanism driving the growth of translocation renal cell carcinoma (tRCC), a especially aggressive cancer affecting children and adolescents, and developed a potential therapeutic strategy to disrupt it. the study, conducted at Texas A&M University, reveals that cancer-driving fusion proteins hijack RNA to form cellular “droplet hubs” that fuel tumor growth, and demonstrates a method to dismantle these hubs, effectively halting cancer progression in laboratory models.
tRCC accounts for nearly 30% of renal cancers in children and adolescents,but current treatment options are limited and frequently enough yield poor outcomes.The research, published and highlighted by Texas A&M University’s *Vital Record*, sheds light on *how* this cancer organizes its growth machinery, offering a new avenue for therapeutic intervention.
The team discovered that TFE3 oncofusions – abnormal proteins created by gene rearrangements – aren’t acting alone. They actively recruit RNA into concentrated droplets within the cell.These droplets aren’t simply byproducts of cellular activity; they actively *reinforce* the droplets, making them even more powerful engines for tumor growth.
To understand this process, researchers employed a suite of advanced molecular biology techniques: CRISPR gene editing to track protein location, SLAM-seq to measure gene activity during droplet formation, CUT&Tag and RIP-seq to map protein-DNA/RNA interactions, and proteomics to identify proteins within the droplets. This layered approach pinpointed PSPC1 as a key partner in the process.
“By mapping how these fusion proteins interact with RNA and other cellular partners, we are not only explaining why this cancer is so aggressive but also revealing weak spots that can be therapeutically exploited,” explained Lei guo, research assistant professor at the Institute of Biosciences and Technology.
Crucially, the team then developed a method to disrupt these “droplet hubs.” They engineered a nanobody-based chemogenetic tool – a designer molecular switch. This tool utilizes a miniature antibody fragment (nanobody) fused to a ”dissolver” protein. The nanobody specifically targets the cancer-driving fusion proteins, and when activated by a chemical trigger, the dissolver protein breaks apart the droplets.
The results were promising. Tumor growth was significantly inhibited in both lab-grown cancer cells and in mouse models.
“This is exciting because tRCC has very few effective treatment options today,” said Yubin Zhou, professor and director of the Center for Translational Cancer Research. “Targeting condensate formation gives us a brand-new angle to attack the cancer, one that traditional drugs have not addressed. It opens the door to therapies that are much more precise and potentially less toxic.”
The researchers believe this strategy coudl extend beyond tRCC, as many pediatric cancers are also driven by fusion proteins.The ability to dissolve these condensates could represent a broadly applicable approach to disrupt cancer growth at its source.
“This research highlights the power of basic science to generate new hope for young patients facing devastating diseases,” added Huang.*Source: Texas A&M University*
