胶质母细胞瘤（GBM）是原发性脑肿瘤中最具侵袭性的形式。由于癌症的浸润性，完全手术切除 GBM 几乎是不可能的。虽然诊断后没有发现最近选择事件的证据，但控制神经胶质瘤发生的选择力很强，在最初进展为恶性肿瘤期间塑造了肿瘤的细胞组成，并对侵袭性和治疗反应产生了后期影响。我们提出了一个数学模型，考虑到神经胶质瘤的倍性水平和脑组织微环境（TME）的性质，模拟神经胶质瘤的生长和侵袭，并用它来推断 GBM 的启动和对标准护理的反应治疗。我们通过整合原发性和复发性 GBM 的计算机模拟、多组学数据和图像分析来近似 TME 中资源访问的空间分布。在癌前环境中，我们的计算机模拟结果表明，低倍性癌细胞对饥饿诱导的细胞死亡具有更强的抵抗力。在恶性环境中，在第一次和第二次手术之间，具有不同倍性组成的模拟肿瘤以不同的速率进展。然而，较高的倍性是否预示着快速复发，取决于 TME。历史数据支持这种对 TME 资源的依赖，如人体组织中葡萄糖摄取率中值与相应组织中出现的癌症类型中值倍性之间的显着相关性所示（Spearman r = -0.70；P = 0.026）。总而言之，我们的研究结果表明，TME 中代谢底物的可用性驱动着具有不同倍性的癌细胞的不同细胞命运决定，并塑造了 GBM 疾病的起始和复发特征。

Glioblastoma (GBM) is the most aggressive form of primary brain tumor. Complete surgical resection of GBM is almost impossible due to the infiltrative nature of the cancer. While no evidence for recent selection events have been found after diagnosis, the selective forces that govern gliomagenesis are strong, shaping the tumor's cell composition during the initial progression to malignancy with late consequences for invasiveness and therapy response. We present a mathematical model that simulates the growth and invasion of a glioma, given its ploidy level and the nature of its brain tissue micro-environment (TME), and use it to make inferences about GBM initiation and response to standard-of-care treatment. We approximate the spatial distribution of resource access in the TME through integration of in-silico modelling, multi-omics data and image analysis of primary and recurrent GBM. In the pre-malignant setting, our in-silico results suggest that low ploidy cancer cells are more resistant to starvation-induced cell death. In the malignant setting, between first and second surgery, simulated tumors with different ploidy compositions progressed at different rates. Whether higher ploidy predicted fast recurrence, however, depended on the TME. Historical data supports this dependence on TME resources, as shown by a significant correlation between the median glucose uptake rates in human tissues and the median ploidy of cancer types that arise in the respective tissues (Spearman r = -0.70; P = 0.026). Taken together our findings suggest that availability of metabolic substrates in the TME drives different cell fate decisions for cancer cells with different ploidy and shapes GBM disease initiation and relapse characteristics.