对癌症多药治疗的连续耐药水平进行建模
Modeling continuous levels of resistance to multidrug therapy in cancer
摘要：
多药耐药是一系列涉及多因素和复杂过程的遗传和表观遗传改变，是成功治疗癌症的挑战。伴随着生物技术和高维数据分析技术的进步，在建模生物系统的连续表型结构模型带来了新的机会，我们研究了一个癌细胞群体模型，考虑了多维连续耐药性状的多药耐药性调查。我们比较了我们的连续抗性性状模型与经典模型，假设一个离散的抗性状态和分类的情况下，连续和离散模型产生不同的动态模式，在新兴的异质性响应药物。我们还计算了各种连续体模型的最大适应性抗性性状，并研究了表突变的影响。最后，我们展示了我们的方法如何可以用来研究肿瘤生长的周转率和增殖分数，并表明，一个连续的阻力水平可能会导致不同的动态相比，其他离散模型的预测。
英文摘要：
Multidrug resistance consists of a series of genetic and epigenetic alternations that involve multifactorial and complex processes, which are a challenge to successful cancer treatments. Accompanied by advances in biotechnology and high-dimensional data analysis techniques that are bringing in new opportunities in modeling biological systems with continuous phenotypic structured models, we study a cancer cell population model that considers a multi-dimensional continuous resistance trait to multiple drugs to investigate multidrug resistance. We compare our continuous resistance trait model with classical models that assume a discrete resistance state and classify the cases when the continuum and discrete models yield different dynamical patterns in the emerging heterogeneity in response to drugs. We also compute the maximal fitness resistance trait for various continuum models and study the effect of epimutations. Finally, we demonstrate how our approach can be used to study tumor growth regarding the turnover rate and the proliferating fraction, and show that a continuous resistance level may result in a different dynamics when compared with the predictions of other discrete models.
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