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.

最初健康的组织细胞积累了几种特定的突变或其他基因改变后，癌症就开始了。由于涉及多种生化和生物物理过程，肿瘤形成的动力学是一个非常复杂的现象。它导致了在标志着癌症开始的所有突变最终固定的道路上存在大量可能的途径，从而使对肿瘤形成的微观机制的理解复杂化。我们提出了一个新的理论框架，通过探索过程的有效自由能景观的特性来分析癌症起始动力学。有人认为，尽管系统中所有突变的固定有许多可能的途径，但在肿瘤形成的道路上只有少数主要途径。使用分析计算和蒙特卡罗计算机模拟，在仅具有两个突变的系统中明确测试了理论方法。大范围的参数与理论预测非常一致，支持了我们的假设，并使我们能够更好地理解癌症发生的机制。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。