Why one-size-fits-all vaso-modulatory interventions fail to control glioma invasion: in silico insights
Why one-size-fits-all vaso-modulatory interventions fail to control glioma invasion: in silico insights
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DOI：
10.1038/srep37283
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发表时间：
2016-11-23
影响因子：
4.6
通讯作者：
Hatzikirou, H.
中科院分区：
文献类型：
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作者：
Alfonso, J. C. L.;Koehn-Luque, A.;Hatzikirou, H.
神经胶质瘤是一种高度侵袭性脑肿瘤，其特征是预后不良和对治疗的反应有限。关于血管调节干预措施对抗神经胶质瘤侵袭的治疗潜力一直存在争论。重要的血管靶向治疗涉及肿瘤血管恶化和正常化。前者针对血管闭塞/塌陷引起的肿瘤梗塞和营养缺乏。相反，使异常肿瘤脉管系统正常化的治疗目的是提高常规治疗方式的疗效。尽管这些策略已显示出治疗潜力，但仍不清楚为什么它们常常无法控制神经胶质瘤的生长。为了阐明这个问题，我们提出了一个基于神经胶质瘤细胞迁移/增殖二分法的数学模型，以研究为什么血管调节干预措施在肿瘤清除方面显示出有限的成功。我们发现存在一个关键的细胞增殖/扩散比率，它将神经胶质瘤对血管调节干预的反应分为两种不同的状态。对于属于一种状态的肿瘤，血管调节降低了前沿速度并增加了浸润宽度，而对于另一种状态的肿瘤，侵袭速度增加而浸润宽度减小。我们讨论如何利用这些计算机结果来指导个体化血管调节方法以提高治疗成功率。
Gliomas are highly invasive brain tumours characterised by poor prognosis and limited response to therapy. There is an ongoing debate on the therapeutic potential of vaso-modulatory interventions against glioma invasion. Prominent vasculature-targeting therapies involve tumour blood vessel deterioration and normalisation. The former aims at tumour infarction and nutrient deprivation induced by blood vessel occlusion/collapse. In contrast, the therapeutic intention of normalising the abnormal tumour vasculature is to improve the efficacy of conventional treatment modalities. Although these strategies have shown therapeutic potential, it remains unclear why they both often fail to control glioma growth. To shed some light on this issue, we propose a mathematical model based on the migration/proliferation dichotomy of glioma cells in order to investigate why vaso-modulatory interventions have shown limited success in terms of tumour clearance. We found the existence of a critical cell proliferation/diffusion ratio that separates glioma responses to vaso-modulatory interventions into two distinct regimes. While for tumours, belonging to one regime, vascular modulations reduce the front speed and increase the infiltration width, for those in the other regime, the invasion speed increases and infiltration width decreases. We discuss how these in silico findings can be used to guide individualised vaso- modulatory approaches to improve treatment success rates.