Cell Press highlights new cancer therapy
- Researchers at the MRC Laboratory of Medical Sciences and Imperial College London reported a new weakness in RAS-driven cancers: their overloaded RNA spliceosome. - In Nature Communications, the team identified six essential spliceosome components, including SF3B1 and RBM39, and shrank RAS-driven liver tumors in mice. - The work points to a drug target beyond mutant RAS itself, where resistance has limited current therapies. (nature.com)
Cancer cells with RAS mutations appear to rely on an overloaded RNA-processing system called the spliceosome, giving researchers a new drug target beyond RAS itself. (nature.com) The study, published April 15 in Nature Communications, was led by Verena Wagner and Laura Bousset at the MRC Laboratory of Medical Sciences and Imperial College London. The paper focused on RAS-driven cancers, which remain hard to treat even after recent gains with some mutation-specific RAS inhibitors. (nature.com) (medicalxpress.com) RNA splicing is the cell’s editing step between DNA and protein production: it cuts out non-coding segments and stitches together the final message. The researchers found that RAS signaling pushes up multiple spliceosome components in both precancerous senescent cells and fully transformed tumors. (nature.com) In the paper’s screening work, six spliceosome components emerged as essential in cells expressing oncogenic RAS, including SF3B1 and RBM39. The team also identified SPT5 as a key mediator of the effects tied to SF3B1. (nature.com) The signal showed up across human and mouse lesions in lung, liver, colorectal, and pancreatic cancers. Those are tumor types where KRAS, NRAS, or HRAS mutations are common and treatment resistance remains a recurring problem. (nature.com) (medicalxpress.com) The mouse data are what gave the study its practical edge. In liver cancer models, inhibitors of RBM39 and SF3B1 were effective against both preneoplastic lesions and aggressive tumors expressing oncogenic RAS. (nature.com) The work also sits inside a larger cancer debate over senescence, the state where damaged cells stop dividing but can keep secreting inflammatory signals. The same research group has described how lingering senescent cells can promote tumor progression and therapy resistance in some settings. (nature.com) (lms.mrc.ac.uk) Researchers said the spliceosome may not be unique to RAS cancers, but the paper argues the dependency is especially strong there. That leaves the next step where many preclinical cancer stories stall: testing whether spliceosome inhibition can be delivered safely enough to move beyond mouse models. (eurekalert.org) (nature.com)
