肿瘤对抗癌治疗的反应不仅取决于细胞固有的治疗敏感性，还取决于与肿瘤微环境的局部相互作用。制造肿瘤基质的成纤维细胞已被证明可以产生旁分泌因子，这些因子可以强烈降低肿瘤细胞对多种靶向治疗的敏感性。此外，高基质/肿瘤比率通常与较差的生存率和降低的治疗反应相关。然而，与对基质介导的耐药性的分子机制的深入了解相反，它对肿瘤逃避治疗根除的能力的影响仍然知之甚少。在很大程度上，这种知识差距反映了解释微环境阻力的空间方面的挑战，特别是在较长的时间范围内。为了解决这个问题，我们将靶向治疗反应的实验动物模型的增殖-死亡动态的空间推论与空间数学模型结合起来。通过这种方法，我们剖析了肿瘤/基质分布、基质效应的大小和距离的影响。虽然所有测试的参数都会影响肿瘤细胞抵抗消除的能力，但肿瘤组织内基质分布的空间模式具有特别强烈的影响。

The response of tumors to anti-cancer therapies is defined not only by cell-intrinsic therapy sensitivities but also by local interactions with the tumor microenvironment. Fibroblasts that make tumor stroma have been shown to produce paracrine factors that can strongly reduce the sensitivity of tumor cells to many types of targeted therapies. Moreover, a high stroma/tumor ratio is generally associated with poor survival and reduced therapy responses. However, in contrast to advanced knowledge of the molecular mechanisms responsible for stroma-mediated resistance, its effect on the ability of tumors to escape therapeutic eradication remains poorly understood. To a large extent, this gap of knowledge reflects the challenge of accounting for the spatial aspects of microenvironmental resistance, especially over longer time frames. To address this problem, we integrated spatial inferences of proliferation-death dynamics from an experimental animal model of targeted therapy responses with spatial mathematical modeling. With this approach, we dissected the impact of tumor/stroma distribution, magnitude and distance of stromal effects. While all of the tested parameters affected the ability of tumor cells to resist elimination, spatial patterns of stroma distribution within tumor tissue had a particularly strong impact.