Uncovering pan-cancer signatures of chemoresistance.

Conserved chemoresistance across cancer types is linked to a proliferative, MYC-driven tumor state with elevated G2/M and S-phase activity, and activation of DNA repair and PI3K/AKT pathways.

• Why it matters: Understanding whether common molecular programs underlie therapy resistance can inform the development of targeted treatments and improve patient outcomes across multiple cancer types.
• What they did: The study integrated single-cell RNA sequencing, spatial transcriptomics, regulatory network modeling, transcription factor binding data, and pharmacologic perturbation across various cancers to identify a shared resistant tumor state centered on MYC activation and SRM expression.
• The result: Inhibiting MYC, SRM, or WNT signaling restored chemotherapy sensitivity and suppressed resistance pathways, highlighting the MYC-SRM axis as a promising, druggable target for overcoming chemoresistance in epithelial cancers.