ArticleiScience2026
Multi-omic integration identifies broad drug resistance mechanisms and strategies to therapeutically reprogram cancer cells.
Article in iScience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
1 citing paper in PubMed.
- HER2-ADC and HER2-TKI Overcomes HER2 Amplification as an Acquired Resistance to Zongertinib - A Case Report.Lung Cancer (Auckland, N.Z.) · 2026Article
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Broad drug resistance arises from diverse transcriptional, metabolic, and genetic adaptations, yet the unifying features that sustain cross-resistant phenotypes remain unclear. We developed an integrative framework combining PRISM drug-response data with transcriptomic, metabolomic, and mutational profiles to define the molecular programs associated with broad resistance and to nominate compounds capable of reversing them. Resistant cell lines exhibited coordinated activation of extracellular matrix remodeling, stress-adaptation pathways, and survival signaling, with NFE2L2 emerging as a central regulatory hub linking upstream mutations to oxidative-stress transcriptional programs. Multi-omic analyses revealed metabolic reprogramming as a conserved feature of resistance, and patient cohort analyses showed that resistance-associated alterations correlated with shorter progression-free survival. Computational perturbagen screening identified compounds predicted to counteract these transcriptional signatures, converging on regulators of NFE2L2 activity. Experimental testing confirmed that rosiglitazone reduced NFE2L2-associated gene expression and re-sensitized resistant cells to chemotherapy, demonstrating a scalable strategy for rational phenotypic reprogramming.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.