论文标题
通过多类分支过程对癌症进化的计算建模
Computational modelling of cancer evolution by multi-type branching processes
论文作者
论文摘要
转移是人类有机体中癌细胞从原发性肿瘤到次要位置的传播,是大多数癌症患者的最终死亡原因。这就是为什么了解转移的演变以成功打击疾病至关重要的原因。我们考虑治疗后的转移癌细胞群(例如化学疗法)。到达不同的环境中,癌细胞可能会改变其寿命和繁殖,因此它们可能会扩散成不同类型。如果治疗有效,则在分支过程的背景下,癌细胞的繁殖是使每个细胞的平均后代小于一个。但是,在细胞分裂周期中可能发生突变。这些突变可以产生一种新的癌细胞类型,该类型对治疗具有抗性。来自这种新类型的癌细胞可能导致非扩展分支过程的上升。上述情况使我们选择了可还原的多类年龄分支过程,作为研究这种复杂结构的渐近行为的相关框架。我们以前的理论结果与等待时间的渐近行为有关,直到首次发生突变体开始非扩展过程,而修饰的危害功能是衡量癌症疾病立即复发的量度。在本文中,这些渐近结果用于开发Python中通过Numpy封装实现的数值方案和算法,以近似相应数量的计算。总而言之,我们的猜想是,在癌症疾病进化和其他复杂细胞种群系统的背景下,这种方法在揭示癌细胞寿命分布的作用中可能是有利的。
Metastasis, the spread of cancer cells from a primary tumor to secondary location(s) in the human organism, is the ultimate cause of death for the majority of cancer patients. That is why, it is crucial to understand metastases evolution in order to successfully combat the disease. We consider a metastasized cancer cell population after medical treatment (e.g. chemotherapy). Arriving in a different environment the cancer cells may change their lifespan and reproduction, thus they may proliferate into different types. If the treatment is effective, in the context of branching processes it means, the reproduction of cancer cells is such that the mean offspring of each cell is less than one. However, it is possible mutations to occur during cell division cycle. These mutations can produce a new cancer cell type, which is resistant to the treatment. Cancer cells from this new type may lead to the rise of a non-extinction branching process. The above scenario leads us to the choice of a reducible multi-type age-dependent branching process as a relevant framework for studying the asymptotic behavior of such complex structures. Our previous theoretical results are related to the asymptotic behavior of the waiting time until the first occurrence of a mutant starting a non-extinction process and the modified hazard function as a measure of immediate recurrence of cancer disease. In the present paper these asymptotic results are used for developing numerical schemes and algorithms implemented in Python via the NumPy package for approximate calculation of the corresponding quantities. In conclusion, our conjecture is that this methodology can be advantageous in revealing the role of the lifespan distribution of the cancer cells in the context of cancer disease evolution and other complex cell population systems, in general.