Dujon Antoine M, Capp Jean-Pascal, Brown Joel S, Pujol Pascal, Gatenby Robert A, Ujvari Beata, Alix-Panabières Catherine, Thomas Frédéric
CREEC/CANECEV, MIVEGEC (CREES), University of Montpellier, CNRS, IRD, 34172 Montpellier, France.
Centre for Integrative Ecology, School of Life and Environmental Sciences, Deakin University, Waurn Ponds, VIC 3216, Australia.
Cancers (Basel). 2021 Jul 22;13(15):3693. doi: 10.3390/cancers13153693.
The majority of cancer-related deaths are the result of metastases (i.e., dissemination and establishment of tumor cells at distant sites from the origin), which develop through a multi-step process classically termed the metastatic cascade. The respective contributions of each step to the metastatic process are well described but are also currently not completely understood. Is there, for example, a critical phase that disproportionately affects the probability of the development of metastases in individual patients? Here, we address this question using a modified Drake equation, initially formulated by the astrophysicist Frank Drake to estimate the probability of the emergence of intelligent civilizations in the Milky Way. Using simulations based on realistic parameter values obtained from the literature for breast cancer, we examine, under the linear progression hypothesis, the contribution of each component of the metastatic cascade. Simulations demonstrate that the most critical parameter governing the formation of clinical metastases is the survival duration of circulating tumor cells (CTCs).
大多数与癌症相关的死亡是转移（即肿瘤细胞从原发部位扩散并在远处形成病灶）的结果，转移通过一个经典的多步骤过程发生，这个过程被称为转移级联反应。虽然转移级联反应的每个步骤对转移过程的具体贡献已有详细描述，但目前仍未完全明晰。例如，是否存在一个关键阶段，它对个体患者发生转移的概率有不成比例的影响？在此，我们使用一个经过修改的德雷克方程来解决这个问题，该方程最初由天体物理学家弗兰克·德雷克提出，用于估计银河系中出现智慧文明的概率。基于从文献中获取的乳腺癌实际参数值进行模拟，我们在线性进展假设下，研究转移级联反应各组成部分的贡献。模拟结果表明，控制临床转移形成的最关键参数是循环肿瘤细胞（CTC）的存活时长。
