ArticleCancer discovery2022
Ontogeny and Vulnerabilities of Drug-Tolerant Persisters in HER2+ Breast Cancer.
Article in Cancer discovery, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
81 citing papers in PubMed, 1 synthesis or guideline pooled it, 109 citations in OpenAlex.
- Cost-effectiveness analysis of the treatment pathway after trastuzumab treatment failure in patients with HER2-positive advanced breast cancer: a chinese health system perspective.BMC health services research · 2026Pooled it
- Targeting an ASCL1-WNT11-ERK feed-forward loop to overcome pyrotinib resistance in HER2-positive breast cancer.Materials today. Bio · 2026Article
- CDK8/19 inhibition prevents adaptive resistance to CDK4/6 inhibitors in vitro and in vivo.Cell reports. Medicine · 2026Article
- BCL11B predetermines a persister state in breast cancer that is reversed by TNFα.Science advances · 2026Article
- Review
- Targeting DNA Polymerase Epsilon Induces Tumor Clearance and Activates an NF-κB-Mediated Inflammatory Response in Triple-Negative Breast Cancer.Cancer research · 2026Article
- LAG3 Gene Therapy Attenuates Autoimmune Uveitis by Regulating the PI3K/Akt Signaling Pathway.Investigative ophthalmology & visual science · 2026Article
- Interleukin-1α-Mediated Activation of TNF-α/NF-κB Signaling Confers Resistance to Osimertinib in EGFR-Mutant Non-Small-Cell Lung Cancer.Thoracic cancer · 2026Article
- Molecular Mechanisms Underlying Recurrence in Triple-Positive Breast Cancer (ER+/PR+/HER2+) and Potential Repurposing of Multi-Target Inhibitors.International journal of molecular sciences · 2026Review
- Impact of variability in cell generation times on cell-to-cell variability of protein concentrations.bioRxiv : the preprint server for biology · 2026Article
- Stochastic Gene Expression Model with State-Dependent Protein Activation Delay.bioRxiv : the preprint server for biology · 2026Article
- Anoikis resistance and metastasis of ovarian cancer can be overcome by CDK8/19 mediator kinase inhibition.JCI insight · 2026Article
- Role of p38 MAPK in the cytokine reprogramming of a human leukemic cell line with a drug-resistant phenotype.Cell communication and signaling : CCS · 2026Article
- Paneth-like transition drives resistance to dual targeting of KRAS and EGFR in colorectal cancer.Cancer cell · 2026Article
- Drug-tolerant persister cells: the deadly survivors in hematological malignancies.Frontiers in pharmacology · 2026Review
- Article
- SPP1 + macrophage and Treg interaction mediates immunosuppression and adverse survival in HER2 + breast cancer.Scientific reports · 2025Article
- Drug-tolerant persister cells in cancer: bridging the gaps between bench and bedside.Nature communications · 2025Review
- Characterization of Drug-Tolerant Persister Cells in Triple-Negative Breast Cancer Identifies a Shared Persistence Program across Treatments and Patients.Cancer research · 2025Article
- Targeting Drug-Tolerant Persister Cancer Cells: Can Nanomaterial-Based Strategies Be Helpful for Anti-DTP Therapies?Pharmaceutics · 2025Review
21 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
24 authors at 6 institutions in 3 countries.
Funding
Abstract
Resistance to targeted therapies is an important clinical problem in HER2-positive (HER2+) breast cancer. "Drug-tolerant persisters" (DTP), a subpopulation of cancer cells that survive via reversible, nongenetic mechanisms, are implicated in resistance to tyrosine kinase inhibitors (TKI) in other malignancies, but DTPs following HER2 TKI exposure have not been well characterized. We found that HER2 TKIs evoke DTPs with a luminal-like or a mesenchymal-like transcriptome. Lentiviral barcoding/single-cell RNA sequencing reveals that HER2+ breast cancer cells cycle stochastically through a "pre-DTP" state, characterized by a G0-like expression signature and enriched for diapause and/or senescence genes. Trajectory analysis/cell sorting shows that pre-DTPs preferentially yield DTPs upon HER2 TKI exposure. Cells with similar transcriptomes are present in HER2+ breast tumors and are associated with poor TKI response. Finally, biochemical experiments indicate that luminal-like DTPs survive via estrogen receptor-dependent induction of SGK3, leading to rewiring of the PI3K/AKT/mTORC1 pathway to enable AKT-independent mTORC1 activation. SIGNIFICANCE: DTPs are implicated in resistance to anticancer therapies, but their ontogeny and vulnerabilities remain unclear. We find that HER2 TKI-DTPs emerge from stochastically arising primed cells ("pre-DTPs") that engage either of two distinct transcriptional programs upon TKI exposure. Our results provide new insights into DTP ontogeny and potential therapeutic vulnerabilities. This article is highlighted in the In This Issue feature, p. 873.
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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 OpenQuestion graph.