Department of Chemistry, Rice University, Houston, Texas; Center for Theoretical Biological Physics, Rice University, Houston, Texas.
Department of Chemistry, Rice University, Houston, Texas.
Biophys J. 2022 Oct 4;121(19):3698-3705. doi: 10.1016/j.bpj.2022.05.011. Epub 2022 May 14.
Cancer starts after initially healthy tissue cells accumulate several specific mutations or other genetic alterations. The dynamics of tumor formation is a very complex phenomenon due to multiple involved biochemical and biophysical processes. It leads to a very large number of possible pathways on the road to final fixation of all mutations that marks the beginning of the cancer, complicating the understanding of microscopic mechanisms of tumor formation. We present a new theoretical framework of analyzing the cancer initiation dynamics by exploring the properties of effective free-energy landscape of the process. It is argued that although there are many possible pathways for the fixation of all mutations in the system, there are only a few dominating pathways on the road to tumor formation. The theoretical approach is explicitly tested in the system with only two mutations using analytical calculations and Monte Carlo computer simulations. Excellent agreement with theoretical predictions is found for a large range of parameters, supporting our hypothesis and allowing us to better understand the mechanisms of cancer initiation. Our theoretical approach clarifies some important aspects of microscopic processes that lead to tumor formation.
癌症始于最初健康的组织细胞积累了几个特定的突变或其他遗传改变。由于涉及多个生化和生物物理过程，肿瘤形成的动态是一个非常复杂的现象。这导致了在最终固定所有突变的道路上有非常多的可能途径，这些突变标志着癌症的开始，从而使肿瘤形成的微观机制的理解变得复杂。我们通过探索过程的有效自由能景观的特性，提出了一种新的分析癌症起始动力学的理论框架。有人认为，尽管在系统中有许多可能的途径可以固定所有突变，但在肿瘤形成的道路上只有少数主导途径。该理论方法在仅包含两个突变的系统中使用解析计算和蒙特卡罗计算机模拟进行了明确的测试。在很大的参数范围内都发现了与理论预测的极好一致性，这支持了我们的假设，并使我们能够更好地理解癌症起始的机制。我们的理论方法阐明了导致肿瘤形成的微观过程的一些重要方面。
