靶向药物耐受持久细胞：突破HER2阳性胃癌治疗瓶颈的新前沿
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TL;DR - This clinical review presents drug-tolerant persister (DTP) cells as a key non-genetic driver of relapse and acquired resistance in HER2-positive gastric cancer. Targeting their metabolic, signaling, and epigenetic vulnerabilities could extend responses to anti-HER2 therapies, although clinical evidence remains limited.
- DTP cells survive treatment in a reversible, slow-growing state and may seed minimal residual disease, recurrence, and stable acquired resistance.
- HER2 heterogeneity, bypass signaling through EGFR/HER3 and PI3K/AKT/mTOR or MAPK pathways, metabolic adaptation, and an immunosuppressive microenvironment support DTP survival.
- Proposed strategies include inducing ferroptosis through GPX4-related vulnerabilities, co-targeting survival pathways such as PI3K, WEE1, or FAK-YAP, and disrupting epigenetic plasticity.
- Translation is constrained by the lack of DTP-specific biomarkers and uncertainty over whether intervention should prevent DTP formation or eliminate residual cells after response.
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靶向药物耐受持久细胞：突破HER2阳性胃癌治疗瓶颈的新前沿
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TL;DR - This clinical review presents drug-tolerant persister (DTP) cells as a key non-genetic driver of relapse and acquired resistance in HER2-positive gastric cancer. Targeting their metabolic, signaling, and epigenetic vulnerabilities could extend responses to anti-HER2 therapies, although clinical evidence remains limited.
- DTP cells survive treatment in a reversible, slow-growing state and may seed minimal residual disease, recurrence, and stable acquired resistance.
- HER2 heterogeneity, bypass signaling through EGFR/HER3 and PI3K/AKT/mTOR or MAPK pathways, metabolic adaptation, and an immunosuppressive microenvironment support DTP survival.
- Proposed strategies include inducing ferroptosis through GPX4-related vulnerabilities, co-targeting survival pathways such as PI3K, WEE1, or FAK-YAP, and disrupting epigenetic plasticity.
- Translation is constrained by the lack of DTP-specific biomarkers and uncertainty over whether intervention should prevent DTP formation or eliminate residual cells after response.