Therapy-induced plasticity in glioblastoma胶质母细胞瘤的治疗诱导可塑性
Review pending待审阅 Version 0.1.0 · status: draft · last expert review: not yet reviewed版本 0.1.0 · 状态：初稿 · 最近专家审阅：尚未审阅
Research question研究问题
- Does glioblastoma change cell state after radiotherapy and chemotherapy?放化疗后胶质母细胞瘤的细胞状态会改变吗？
- Is GBM recurrence driven by new mutations or by phenotype switching?GBM 复发由新突变驱动还是由表型转换驱动？
- Can virtual cells predict therapy-induced state transitions?虚拟细胞能预测治疗诱导的状态转变吗？
Current understanding当前认识
Evidence in the library suggests that GBM cells shift state under therapy — recurrent tumors show a mesenchymal shift, and radiotherapy rewires responses to genetic perturbations in mouse models. Whether these shifts can be predicted computationally has not yet been demonstrated.文献库证据提示 GBM 细胞在治疗下会发生状态转变——复发肿瘤表现出间充质转变，小鼠模型中放疗会重塑细胞对基因扰动的反应。这些转变能否被计算预测尚未得到证明。
A multi-omic study of 86 patient-matched primary–recurrent GBM pairs found a shift to a mesenchymal phenotype at recurrence. The authors note that longitudinal studies show no apparent selection for specific DNA mutations, suggesting phenotype switching rather than genetic evolution as an escape mechanism — a hypothesis, not a settled conclusion.一项针对 86 对患者配对原发-复发 GBM 的多组学研究发现复发时向间充质表型转变。作者指出纵向研究未见特定 DNA 突变的明显选择，提示逃逸机制可能是表型转换而非遗传进化——这是假说，而非定论。 VC0069
In mouse GBM models, an in vivo Perturb-seq CRISPRi platform showed that radiotherapy rewires transcriptional responses to genetic perturbations in an in vivo-dependent manner, with heterogeneous sensitisation or resistance.在小鼠 GBM 模型中，体内 Perturb-seq CRISPRi 平台显示放疗以依赖体内环境的方式重塑细胞对基因扰动的转录反应，表现出异质性的增敏或耐药。 VC0070
Specific regulators of plasticity under therapy include BRD2, whose bromodomain loss reversed MES transition and increased radiation sensitivity in xenografts, and immune–cancer interactions that drive MES-like transitions; a preprint proposes that spatial epigenomic niches set the likelihood of a cell being in one state or another.治疗下可塑性的具体调控因素包括 BRD2（其溴结构域缺失可在异种移植中逆转 MES 转变并提高放射敏感性）以及驱动 MES 样转变的免疫-癌细胞相互作用；一项预印本提出空间表观基因组生态位决定细胞处于某一状态的可能性。 VC0095 VC0066 VC0093 · preprint · 预印本
Modelling status: tissue-scale models address treatment (reinforcement-learning scheduling on a multiscale mechanistic model; TumorTwin radiotherapy-response demonstration), and DELPHAI (preprint) predicts temozolomide responses in organoids, but no model in the library has been validated to predict therapy-induced cell-state transitions in patients.建模现状：组织尺度模型涉及治疗（基于多尺度机制模型的强化学习排程；TumorTwin 的放疗反应演示），DELPHAI（预印本）可预测类器官的替莫唑胺反应，但文献库中尚无模型经验证可预测患者体内治疗诱导的细胞状态转变。 VC0073 VC0134 VC0129 · preprint · 预印本
Evidence map证据图谱
Primary studies & datasets原始研究与数据集
- VC0069 A single-cell atlas of glioblastoma evolution under therapy reveals cell-intrinsic and cell-extrinsic therapeutic targets. — Wang L, Jung J, Babikir H, Shamardani K, Jain S, Feng X, Gupta N, Rosi S, Chang S, Raleigh D, Solomon D, Phillips JJ, Diaz AA., Nature cancer, 2022
- VC0095 BRD2 bromodomain-mediated regulation of cell state plasticity modulates therapy response in glioblastoma. — Vadla R et al., Neuro-oncology, 2025
- VC0066 Interactions between cancer cells and immune cells drive transitions to mesenchymal-like states in glioblastoma. — Hara T et al., Cancer cell, 2025
- VC0093 · preprint · 预印本 Spatial epigenomic niches underlie glioblastoma cell state plasticity — Kint S et al., bioRxiv, 2025
- VC0089 A longitudinal single-cell and spatial multiomic atlas of pediatric high-grade glioma. — Sussman JH et al., Cell reports. Medicine, 2026
- VC0059 An Integrative Model of Cellular States, Plasticity, and Genetics for Glioblastoma. — Neftel C et al., Cell, 2019
Related models & tools相关模型与工具
- VC0073 Multiscale mathematical model-informed reinforcement learning optimizes combination treatment scheduling in glioblastoma evolution. — Liu Z, Zhang J, Hong L, Nie Q, Sun X., Science advances, 2025
- VC0134 TumorTwin: a Python framework for patient-specific digital twins in oncology — Kapteyn et al., BMC Med Inform Decis Mak, 2026
- VC0129 · preprint · 预印本 DELPHAI, AI Agent for Predicting Drug Response and Resistance — Peng et al., preprint, 2025
- VC0132 Drug and single-cell gene expression integration identifies sensitive and resistant glioblastoma cell populations — Suter et al., Nature Communications, 2026
Perturbation & validation evidence扰动与验证证据
- VC0070 In vivo perturb-seq of cancer and microenvironment cells dissects oncologic drivers and radiotherapy responses in glioblastoma. — Liu SJ et al., Genome biology, 2024
- VC0097 Automated and personalized glioblastoma tumor organoid drug screening platform exposes sensitivity to proteasome and HDAC inhibitors. — Jungwirth G et al., NPJ precision oncology, 2026
- VC0048 Deep-learning-based gene perturbation effect prediction does not yet outperform simple linear baselines. — Ahlmann-Eltze C, Huber W, Anders S., Nature methods, 2025
13 library items cited on this page; 2 are preprints (not peer reviewed).本页引用文献库条目 13 条，其中预印本（未经同行评审）2 条。
What remains uncertain尚不确定之处
Perturb-seq radiotherapy findings come from mouse models and may not transfer to human tumors.Perturb-seq 放疗结论来自小鼠模型，未必能外推到人体肿瘤。 VC0070
Induction versus selection of states at recurrence remains unresolved.复发时状态是被诱导还是被筛选，仍未解决。 VC0069
Temozolomide-specific single-cell perturbation data are scarce; the main GBM organoid TMZ modelling item is a preprint.替莫唑胺特异的单细胞扰动数据稀缺；主要的 GBM 类器官 TMZ 建模条目为预印本。 VC0129 · preprint · 预印本
Pediatric high-grade glioma longitudinal data exist but may follow different dynamics than adult GBM.儿童高级别胶质瘤已有纵向数据，但其动态可能与成人 GBM 不同。 VC0089
For research and education only. Not medical advice and not a recommendation of any diagnosis, treatment or product. Patients should consult their own physicians.仅供科研与教育参考，不构成医疗建议，也不构成对任何诊疗或产品的推荐。患者请咨询主治医生。