ArticleNature communications2020
Resistance to targeted therapies as a multifactorial, gradual adaptation to inhibitor specific selective pressures.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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
88 citing papers in PubMed, 133 citations in OpenAlex.
- Evolutionary Antifragile Therapy Is a Treatment Strategy to Suppress Drug Resistance by Exploiting Dose-Response Convexity.Cancer research · 2026Article
- Targeting the cancer metabolism-immunity interface: update and perspectives.Experimental hematology & oncology · 2026Review
- ESR1 mutations and CDK4/6 inhibitor choice shape clonal selection and adaptive cell states during acquired resistance.Genome medicine · 2026Article
- Pre-existing cell states predict resistance to multiple treatments.Cell genomics · 2026Article
- Multifactorial sheltering in peristromal niches shapes in vivo responses of lung cancers to targeted therapies.Nature communications · 2026Article
- Review
- Bidirectional coupling among EMT, AXL-RB1 signaling and lineage switch drives resistance to osimertinib and worse clinical outcomes in NSCLC.bioRxiv : the preprint server for biology · 2026Article
- Review
- RET Signaling Pathway in Human Cancer: Oncogenic Mechanisms, Selective Inhibitors, and Emerging Resistance Strategies.International journal of molecular sciences · 2026Review
- Pyrimidine-based compounds as promising anticancer agents targeting tumor cell senescence.Molecular therapy. Oncology · 2026Article
- Growth rate-driven modelling suggests that phenotypic adaptation drives drug resistance in BRAFV600E-mutant melanoma.Communications biology · 2026Article
- Multiplexed enrichment and tracking of lineages with CloneSweeper.bioRxiv : the preprint server for biology · 2026Article
- Integrated single-cell and bulk transcriptomic analyses reveal cDC1-centered ubiquitination dysregulation and identify UBE2F as a critical regulator in sepsis.Frontiers in immunology · 2026Article
- Case Report: Short-term disease control with subsequent icotinib therapy in EGFR L858R/C797S, T790M-negative lung adenocarcinoma after osimertinib resistance.Frontiers in oncology · 2026Article
- Editorial: Epigenetic alterations in tumors and therapeutic resistance.Frontiers in genetics · 2026Article
- Multidimensional tumor heterogeneity and its role in therapeutic resistance.Frontiers in immunology · 2026Review
- The Transcriptional Role of Circular RNAs in Drug Resistance by Modulating the miRNA/mRNA Axis.Experientia supplementum (2012) · 2026Article
- A Systematic Review of Evidence for the Cost of Therapeutic Resistance in Cancer.bioRxiv : the preprint server for biology · 2025Article
- MET signaling drives acquired resistance to erdafitinib in muscle-invasive bladder cancer cells.Cell death & disease · 2025Article
- Drug-tolerant persister cells in cancer: bridging the gaps between bench and bedside.Nature communications · 2025Review
28 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 4 institutions in 3 countries.
Funding
Abstract
Despite high initial efficacy, targeted therapies eventually fail in advanced cancers, as tumors develop resistance and relapse. In contrast to the substantial body of research on the molecular mechanisms of resistance, understanding of how resistance evolves remains limited. Using an experimental model of ALK positive NSCLC, we explored the evolution of resistance to different clinical ALK inhibitors. We found that resistance can originate from heterogeneous, weakly resistant subpopulations with variable sensitivity to different ALK inhibitors. Instead of the commonly assumed stochastic single hit (epi) mutational transition, or drug-induced reprogramming, we found evidence for a hybrid scenario involving the gradual, multifactorial adaptation to the inhibitors through acquisition of multiple cooperating genetic and epigenetic adaptive changes. Additionally, we found that during this adaptation tumor cells might present unique, temporally restricted collateral sensitivities, absent in therapy naïve or fully resistant cells, suggesting the potential for new therapeutic interventions, directed against evolving resistance.
Indexed as
Identifiers
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.