Overview
- Cold Spring Harbor researchers mapped an SRSF1–AURKA–MYC feedback loop that drives aggressive PDAC progression.
- SRSF1 promotes an AURKA splicing pattern that boosts AURKA, which stabilizes MYC, reinforcing SRSF1 to sustain the loop.
- From 12 antisense oligonucleotides, a lead candidate, ASO-A, forced AURKA exon skipping, collapsed the circuit, and triggered apoptosis in tumor cells.
- The approach reduced viability in PDAC cell models and human patient-derived organoids, offering a potential complement to KRAS-targeted therapies.
- The findings, published in Molecular Cell, come as the Krainer lab continues optimizing the ASO before further preclinical work and any consideration of clinical testing.