Loading
Life sciences · Journal article
Genome Medicine · September 16, 2026
No summary has been generated for this record yet. What follows is drawn from its source metadata only.
Journal article.
No findings were extractable from the material analysed.
Safety was not reported in the material analysed. Check the source before drawing any conclusion about harm.
The source did not state who this applies to in practice.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
This record has not been graded across any dimension yet. Treat the label above as provisional and read the source.
What is missing. This record has no bottom line, key findings, reported figures, evidence dimensions. That is a gap in the analysis, not a judgement about the study.
Abstract Background Chemotherapy resistance remains a formidable challenge in cancer treatment, driving high mortality rates worldwide. Despite significant advancements, it remains unclear whether conserved molecular programs underpin therapy resistance across cancer types. Methods Here, we integrate single-cell RNA sequencing, spatial transcriptomics, regulatory network modeling, transcription factor binding data, and pharmacologic perturbation across multiple cancer types to define a conserved, proliferative chemoresistant tumor state. Results Contrary to the prevailing notion that resistance arises from quiescent or EMT-like phenotypes, we find that resistant tumor cells display elevated G2/M and S-phase activity, enriched expression of E2F and MYC target genes, and activation of DNA repair and PI3K/AKT signaling pathways. We identify the transcription factor MYC as a central regulator of the resistant state, with progressive activation along the resistance trajectory and focal expression in resistant epithelial niches. A novel MYC target, SRM (Spermidine Synthase), emerges as a conserved effector of resistance, promoting polyamine biosynthesis critical for chromatin stability and metabolic resilience. SRM expression correlates with MYC binding and predicts poor patient survival. Functional validation in cell lines, patient-derived organoids and mouse models demonstrate that pharmacologic inhibition of MYC, SRM, or WNT signalling restores chemotherapy sensitivity, suppresses resistance-associated pathways, and reactivates apoptosis. Spatial and survival analyses confirm the clinical relevance of the MYC–SRM axis, establishing it as a druggable module in treatment-refractory cancers. Conclusions To our knowledge, this is the first comprehensive study that redefines chemoresistance as a proliferative, MYC-driven state and uncover SRM as a tractable vulnerability, offering new avenues for therapeutic intervention across diverse epithelial malignancies.