ArticleNature genetics2020
Using antagonistic pleiotropy to design a chemotherapy-induced evolutionary trap to target drug resistance in cancer.
Article in Nature genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 89 citations in OpenAlex.
- Clinical utility of PDX cohorts to reveal biomarkers of intrinsic resistance and clonal architecture changes underlying acquired resistance to cetuximab in HNSCC.Signal transduction and targeted therapy · 2022Trial
- CRISPR-activation reveals key resistance genes and vulnerabilities of copy number variants inbioRxiv : the preprint server for biology · 2026Article
- SUMOylation enhances DNMT1 function to repress mega-intergenic RNAs and viral mimicry.Nature genetics · 2026Article
- Article
- Combined Inhibition of HRAS and MEK Induces Tumor Regression and Restores Myogenic Differentiation in HRAS-Mutant Rhabdomyosarcoma.Cancer research · 2026Article
- Epigenetic modifications in cancer drug resistance: molecular mechanisms and therapeutic interventions.Molecular biomedicine · 2026Review
- Characterization and therapeutic suppression of KEAP1-NRF2-driven resistance to KRAS inhibitors in pancreatic and lung cancer.bioRxiv : the preprint server for biology · 2026Article
- CRISPR-Cas9 Screening Identifies Resistance Mechanisms to KRAS Inhibition in Pancreatic Cancer.Cancer research · 2026Article
- EGFR inhibitor-resistant lung cancers exhibit collateral sensitivity to a covalent, cysteine-independent KEAP1 oligomerizing molecular bridge.Nature communications · 2026Article
- cellMCD Effectively Discovers Drug Resistance and Sensitivity Genes for Acute Myeloid Leukemia.Genes · 2026Article
- MYC in cancer: from undruggable target to clinical trials.Nature reviews. Drug discovery · 2025Review
- Targeting phosphatidylserine in tumor cell membranes with a zinc-containing molecule to efficiently combat tumor metastasis.Journal of nanobiotechnology · 2025Article
- Programming tumor evolution with selection gene drives to proactively combat drug resistance.Nature biotechnology · 2025Article
- Concurrent Inhibition of the RAS-MAPK Pathway and PIKfyve Is a Therapeutic Strategy for Pancreatic Cancer.Cancer research · 2025Article
- Genome-wide CRISPR/Cas9 screen identifies AraC-daunorubicin-etoposide response modulators associated with outcomes in pediatric AML.Blood advances · 2025Article
- Identification and multi-omics analysis of essential coding and long non-coding genes in colorectal cancer.Biochemistry and biophysics reports · 2025Article
- Advances in the application of patient-derived xenograft models in acute leukemia resistance.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Ecological and evolutionary dynamics to design and improve ovarian cancer treatment.Clinical and translational medicine · 2024Review
- Drug dependence in cancer is exploitable by optimally constructed treatment holidays.Nature ecology & evolution · 2024Article
- TEAD Inhibition Overcomes YAP1/TAZ-Driven Primary and Acquired Resistance to KRASG12C Inhibitors.Cancer research · 2023Article
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19 authors at 4 institutions in 3 countries.
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Abstract
Local adaptation directs populations towards environment-specific fitness maxima through acquisition of positively selected traits. However, rapid environmental changes can identify hidden fitness trade-offs that turn adaptation into maladaptation, resulting in evolutionary traps. Cancer, a disease that is prone to drug resistance, is in principle susceptible to such traps. We therefore performed pooled CRISPR-Cas9 knockout screens in acute myeloid leukemia (AML) cells treated with various chemotherapies to map the drug-dependent genetic basis of fitness trade-offs, a concept known as antagonistic pleiotropy (AP). We identified a PRC2-NSD2/3-mediated MYC regulatory axis as a drug-induced AP pathway whose ability to confer resistance to bromodomain inhibition and sensitivity to BCL-2 inhibition templates an evolutionary trap. Across diverse AML cell-line and patient-derived xenograft models, we find that acquisition of resistance to bromodomain inhibition through this pathway exposes coincident hypersensitivity to BCL-2 inhibition. Thus, drug-induced AP can be leveraged to design evolutionary traps that selectively target drug resistance in cancer.
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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.