Computer Science Department, University of Turin, Corso Svizzera 185, Torino, Italy.
BMC Bioinformatics. 2013;14 Suppl 6(Suppl 6):S11. doi: 10.1186/1471-2105-14-S6-S11. Epub 2013 Apr 17.
Cancer stem cell theory suggests that cancers are derived by a population of cells named Cancer Stem Cells (CSCs) that are involved in the growth and in the progression of tumors, and lead to a hierarchical structure characterized by differentiated cell population. This cell heterogeneity affects the choice of cancer therapies, since many current cancer treatments have limited or no impact at all on CSC population, while they reveal a positive effect on the differentiated cell populations.
In this paper we investigated the effect of vaccination on a cancer hierarchical structure through a multi-level model representing both population and molecular aspects. The population level is modeled by a system of Ordinary Differential Equations (ODEs) describing the cancer population's dynamics. The molecular level is modeled using the Petri Net (PN) formalism to detail part of the proliferation pathway. Moreover, we propose a new methodology which exploits the temporal behavior derived from the molecular level to parameterize the ODE system modeling populations. Using this multi-level model we studied the ErbB2-driven vaccination effect in breast cancer.
We propose a multi-level model that describes the inter-dependencies between population and genetic levels, and that can be efficiently used to estimate the efficacy of drug and vaccine therapies in cancer models, given the availability of molecular data on the cancer driving force.
癌症干细胞理论表明，癌症是由一群被称为癌症干细胞（CSCs）的细胞引起的，这些细胞参与肿瘤的生长和进展，并导致具有分化细胞群体特征的层次结构。这种细胞异质性影响癌症治疗的选择，因为许多当前的癌症治疗方法对 CSC 群体的影响有限或根本没有影响，而对分化细胞群体则显示出积极的影响。
在本文中，我们通过一个代表群体和分子方面的多层次模型研究了疫苗接种对癌症层次结构的影响。群体水平通过描述癌症群体动态的常微分方程（ODE）系统进行建模。分子水平使用 Petri 网（PN）形式化来详细描述增殖途径的一部分。此外，我们提出了一种新的方法，利用从分子水平得出的时间行为来参数化描述群体的 ODE 系统。使用这个多层次模型，我们研究了 ErbB2 驱动的乳腺癌疫苗接种效应。
我们提出了一个多层次模型，描述了群体和遗传水平之间的相互依存关系，并且可以有效地用于在癌症模型中估计药物和疫苗治疗的疗效，前提是有关于癌症驱动因素的分子数据。
