Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33136, USA; Department of Molecular and Cellular Pharmacology, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
Case Comprehensive Cancer Center, Cleveland, OH 44195, USA; Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
Trends Cancer. 2024 Jan;10(1):15-27. doi: 10.1016/j.trecan.2023.08.002. Epub 2023 Aug 23.
The Swiss cheese model is used to assess risks and explain accidents in a variety of industries. This model can be applied to dissect the homeostatic mechanisms whose cumulative dysregulation contributes to disease states, including cancer. Using glioblastoma (GBM) as an exemplar, we discuss how specific protumorigenic mechanisms collectively drive disease by affecting genomic integrity, epigenetic regulation, metabolic homeostasis, and antitumor immunity. We further highlight how host factors, such as hormonal differences and aging, impact this process, and the interplay between these 'system failures' that enable tumor progression and foster therapeutic resistance. Finally, we examine therapies that consider the interactions between these elements, which may comprise more effective approaches given the multifaceted protumorigenic mechanisms that drive GBM.
瑞士奶酪模型用于评估各种行业的风险和解释事故。该模型可用于剖析稳态机制，其累积失调导致疾病状态，包括癌症。我们以胶质母细胞瘤 (GBM) 为例，讨论了特定的促瘤机制如何通过影响基因组完整性、表观遗传调控、代谢稳态和抗肿瘤免疫来共同驱动疾病。我们还进一步强调了宿主因素（如激素差异和衰老）如何影响这一过程，以及这些“系统故障”之间的相互作用，这些相互作用使肿瘤进展并促进治疗耐药性。最后，我们研究了考虑这些因素相互作用的治疗方法，鉴于驱动 GBM 的多方面促瘤机制，这些方法可能构成更有效的方法。
