ArticleNature cancer2021
IRS1 phosphorylation underlies the non-stochastic probability of cancer cells to persist during EGFR inhibition therapy.
Article in Nature cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 20 citations in OpenAlex.
- Chemoresistome mapping in individual breast cancer patients unravels diversity in dynamic transcriptional adaptation.Molecular oncology · 2025Article
- Drug-tolerant persister cells in cancer: bridging the gaps between bench and bedside.Nature communications · 2025Review
- Eradicating Drug-tolerant Persister Cells in EGFR-Mutated Non-Small Cell Lung Cancer by Targeting TROP2 with CAR-T Cellular Therapy.Cancer discovery · 2025Article
- Epigenomic analysis identifies DTP subpopulation using HOPX to develop targeted therapy resistance in lung adenocarcinoma.iScience · 2025Article
- Impact of 4-Environment & health (Washington, D.C.) · 2025Article
- Integrating multiscale mathematical modeling and multidimensional data reveals the effects of epigenetic instability on acquired drug resistance in cancer.PLoS computational biology · 2025Article
- Cancer drug-tolerant persister cells: from biological questions to clinical opportunities.Nature reviews. Cancer · 2024Review
- Targeting therapy-persistent residual disease.Nature cancer · 2024Review
- Drug tolerant persister cell plasticity in cancer: A revolutionary strategy for more effective anticancer therapies.Signal transduction and targeted therapy · 2024Review
- Drug-tolerant persister cancer cells.Journal of the National Cancer Center · 2024Article
- Drug-tolerant persister cells in cancer: the cutting edges and future directions.Nature reviews. Clinical oncology · 2023Review
- Resistance of Lung Cancer to EGFR-Specific Kinase Inhibitors: Activation of Bypass Pathways and Endogenous Mutators.Cancers · 2023Review
- Methylation across the central dogma in health and diseases: new therapeutic strategies.Signal transduction and targeted therapy · 2023Review
- Pharmaceutical Reactivation of Attenuated Apoptotic Pathways Leads to Elimination of Osimertinib Drug-Tolerant Cells.Cancer research communications · 2022Article
- A heritable, non-genetic road to cancer evolution.Nature · 2022Article
Corrections and comments
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Authors and funding
26 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Stochastic transition of cancer cells between drug-sensitive and drug-tolerant persister phenotypes has been proposed to play a key role in non-genetic resistance to therapy. Yet, we show here that cancer cells actually possess a highly stable inherited chance to persist (CTP) during therapy. This CTP is non-stochastic, determined pre-treatment and has a unimodal distribution ranging from 0 to almost 100%. Notably, CTP is drug specific. We found that differential serine/threonine phosphorylation of the insulin receptor substrate 1 (IRS1) protein determines the CTP of lung and of head and neck cancer cells under epidermal growth factor receptor inhibition, both in vitro and in vivo. Indeed, the first-in-class IRS1 inhibitor NT219 was highly synergistic with anti-epidermal growth factor receptor therapy across multiple in vitro and in vivo models. Elucidation of drug-specific mechanisms that determine the degree and stability of cellular CTP may establish a framework for the elimination of cancer persisters, using new rationally designed drug combinations.
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Registered trials
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