Uncovering pan-cancer signatures of chemoresistance.

Conserved chemoresistance across cancers is driven by a proliferative, MYC-regulated tumor state involving SRM, with over 70% of resistant cells showing elevated cell cycle activity.

• Why it matters: Understanding the molecular basis of therapy resistance is crucial for developing effective treatments, as current approaches often fail to target shared resistance mechanisms across diverse cancers.
• What they did: The study integrated single-cell RNA sequencing, spatial transcriptomics, and functional assays across multiple cancer types to identify a common resistant tumor state characterized by MYC activation and increased cell cycle activity.
• The result: Targeting MYC, SRM, or WNT signaling restored chemosensitivity and suppressed resistance pathways, highlighting the MYC-SRM axis as a promising, druggable vulnerability to improve outcomes in resistant cancers.