近年来揭示了许多复杂的机制和相互作用，推动了恶性肿瘤的发展。肿瘤进化是一种框架，将肿瘤发展解释为一种由适者生存驱动的过程，不同性质的肿瘤细胞竞争有限的资源。为了预测肿瘤的进化轨迹，需要了解细胞特性如何在微环境中影响亚群体的适应度，但这通常是难以获得的。组织的计算多尺度建模可以观察肿瘤环境中每个细胞的完整轨迹。在这里，我们建立了一个带有亚细胞分辨率的三维球形肿瘤模型。测量个体细胞的适应度和肿瘤的进化行为，并将其与细胞和环境参数联系起来。细胞的适应度仅受其在肿瘤中的位置影响，而这种位置受我们模型的两个可变参数影响：细胞间黏附和细胞运动性。我们观察到营养独立和静态或动态营养可用性对异质性肿瘤的进化轨迹的影响，在高分辨率的计算模型中进行了量化。无论是否有营养可用，我们都发现低黏附细胞具有适应度优势，对于肿瘤入侵有利。我们发现引入依赖营养的细胞分裂和死亡可以加快进化速度。营养波动可以增加进化速度。我们确定了一个明显的频率域，在该频率域内，进化速度显著高于具有恒定营养供应的肿瘤。这些发现表明，不稳定的营养供应可以加速肿瘤进化，从而促进过渡到恶性状态。

Recent years have revealed a large number of complex mechanisms and interactions that drive the development of malignant tumors. Tumor evolution is a framework that explains tumor development as a process driven by survival of the fittest, with tumor cells of different properties competing for limited available resources. To predict the evolutionary trajectory of a tumor, knowledge of how cellular properties influence the fitness of a subpopulation in the context of the microenvironment is required and is often inaccessible. Computational multiscale-modeling of tissues enables the observation of the full trajectory of each cell within the tumor environment. Here, we model a 3D spheroid tumor with subcellular resolution. The fitness of individual cells and the evolutionary behavior of the tumor are quantified and linked to cellular and environmental parameters. The fitness of cells is solely influenced by their position in the tumor, which in turn is influenced by the two variable parameters of our model: cell-cell adhesion and cell motility. We observe the influence of nutrient independence and static and dynamically changing nutrient availability on the evolutionary trajectories of heterogeneous tumors in a high-resolution computational model. Regardless of nutrient availability, we find a fitness advantage of low-adhesion cells, which are favorable for tumor invasion. We find that the introduction of nutrient-dependent cell division and death accelerates the evolutionary speed. The evolutionary speed can be increased by fluctuations in nutrients. We identify a distinct frequency domain in which the evolutionary speed increases significantly over a tumor with constant nutrient supply. The findings suggest that an unstable supply of nutrients can accelerate tumor evolution and, thus, the transition to malignancy.