ArticleNature2017
Rare cell variability and drug-induced reprogramming as a mode of cancer drug resistance.
Article in Nature, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 757 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
757 citing papers in PubMed, 1 synthesis or guideline pooled it, 1,279 citations in OpenAlex.
- Rebound regrowth phenomenon in patients with pediatric low-grade gliomas treated with MAPK inhibitors - a systematic review.Oncology reviews · 2026Pooled it
- A single-cell lens into the co-evolution of genotypes and phenotypes in cancer.Nature reviews. Cancer · 2026Review
- Dynamic regulation of H3K9 modifications in cancer: pathogenesis and targeted therapies.Biomarker research · 2026Review
- Clonal lineage tracing and parallel multiomics profiling reveal transcriptional heterogeneity induced by ARID1A deficiency.Science advances · 2026Article
- Host chromatin architecture in HPV-driven cervical cancer: molecular mechanisms and therapeutic resistance.Medical oncology (Northwood, London, England) · 2026Review
- Epigenetic reprogramming of lineage switching in cancer.FEBS letters · 2026Review
- Learning stochasticity via a nonparametric approach to state-dependent noise estimation.Nature communications · 2026Article
- Cell-level random splits leak group-owned answers in single-cell benchmarks.bioRxiv : the preprint server for biology · 2026Article
- CDK8/19 inhibition prevents adaptive resistance to CDK4/6 inhibitors in vitro and in vivo.Cell reports. Medicine · 2026Article
- A guide to understanding tumour evolution through the lens of population genetics.Nature reviews. Cancer · 2026Review
- Liquid biopsy: current applications and future directions.Molecular biomedicine · 2026Review
- Epigenetic Repression ofBiomolecules & therapeutics · 2026Article
- Epigenetic Profiling for Early Detection and Treatment Response Monitoring in Non-Small Cell Lung Cancer: Protocol for a Prospective Translational Biomarker Study.JMIR research protocols · 2026Article
- Epithelial-mesenchymal transition in carcinoma: navigating phenotypic states to target resistance and metastasis.Cancer metastasis reviews · 2026Review
- Selective mRNA translation determines adaptative mutability of melanoma cells to anti-BRAF/MEK combination therapy.EMBO molecular medicine · 2026Article
- Charting intratumor heterogeneity from bench to bedside.Nature cancer · 2026Review
- Varying susceptibility of subpopulations along the epithelial-mesenchymal spectrum to undergo EMT.The FEBS journal · 2026Article
- Clonal memory of cell division in humans diverges between healthy haematopoiesis and acute myeloid leukaemia.Nature communications · 2026Article
- Pre-Existing Heterogeneity Predicts Rare Proteostasis-Stress Programs Across Diverse Perturbations.Biology · 2026Article
- Combinatorial in situ cancer vaccines: unlocking broad and enhanced antitumor responses.Signal transduction and targeted therapy · 2026Review
697 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
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- Erratum issued
Authors and funding
17 authors at 3 institutions in 1 country.
Funding
Abstract
Therapies that target signalling molecules that are mutated in cancers can often have substantial short-term effects, but the emergence of resistant cancer cells is a major barrier to full cures. Resistance can result from secondary mutations, but in other cases there is no clear genetic cause, raising the possibility of non-genetic rare cell variability. Here we show that human melanoma cells can display profound transcriptional variability at the single-cell level that predicts which cells will ultimately resist drug treatment. This variability involves infrequent, semi-coordinated transcription of a number of resistance markers at high levels in a very small percentage of cells. The addition of drug then induces epigenetic reprogramming in these cells, converting the transient transcriptional state to a stably resistant state. This reprogramming begins with a loss of SOX10-mediated differentiation followed by activation of new signalling pathways, partially mediated by the activity of the transcription factors JUN and/or AP-1 and TEAD. Our work reveals the multistage nature of the acquisition of drug resistance and provides a framework for understanding resistance dynamics in single cells. We find that other cell types also exhibit sporadic expression of many of these same marker genes, suggesting the existence of a general program in which expression is displayed in rare subpopulations of cells.
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What OpenQuestion holds
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 OpenQuestion graph.