遗传性肿瘤易感综合征的iPSC模型:通往肿瘤进展与早期干预的机制路径
iPSC Models of Hereditary Cancer Predisposition Syndromes: Mechanistic Pathways to Tumour Progression and Early Intervention
DOI: 10.12677/acm.2026.1652027, PDF,   
作者: 甘蓓蓓, 李文亮*:昆明医科大学第二附属医院胃肠外科,云南 昆明;许 宁*:昆明医科大学第一附属医院肿瘤外科,云南 昆明
关键词: 诱导多能干细胞遗传性肿瘤综合征类器官多组学早期生物标志物Induced Pluripotent Stem Cells Hereditary Cancer Syndromes Organoids Multi-Omics Early Biomarkers
摘要: 遗传性肿瘤易感综合征(hereditary cancer predisposition syndromes, HCPS)源于胚系致病性变异,这类变异在肿瘤发生之前的很长阶段内,即可重塑细胞应激反应、基因组维护能力以及组织特异性的稳态调控。传统研究模型——包括经典肿瘤细胞系、动物模型及患者来源的肿瘤类器官——能够较好反映疾病进展期的表型特征,但在解析癌前阶段的早期事件、谱系依赖的分子机制以及患者间差异性方面存在明显局限。诱导多能干细胞(induced pluripotent stem cells, iPSCs)为此提供了一种可扩增且遗传背景明确的研究平台,可与定向分化、类器官、微生理系统(microphysiological systems)以及等基因基因组编辑技术相结合,用于模拟癌前状态、建立基因型与表型之间的因果联系,并评估预防或治疗干预策略的效果。
Abstract: Hereditary cancer predisposition syndromes (HCPS) arise from germline pathogenic variants that reshape cellular stress responses, genome maintenance and tissue-specific homeostasis long before tumour initiation. Conventional research models—including established tumour cell lines, animal models, and patient-derived tumour organoids—can effectively recapitulate phenotypic features of advanced disease stages, but they have clear limitations in elucidating early events during the precancerous stage, lineage-dependent molecular mechanisms, and inter-patient heterogeneity. Induced pluripotent stem cells (iPSCs) provide an expandable, genetically defined platform that can be combined with directed differentiation, organoids, microphysiological systems and isogenic genome editing to model premalignant states, map genotype-to-phenotype links and test preventive or therapeutic strategies.
文章引用:甘蓓蓓, 许宁, 李文亮. 遗传性肿瘤易感综合征的iPSC模型:通往肿瘤进展与早期干预的机制路径[J]. 临床医学进展, 2026, 16(5): 2190-2198. https://doi.org/10.12677/acm.2026.1652027

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