Alajmi Mesfer, Roy Souvik
1 Department of Mathematics, The University of Texas at Arlington, Arlington, TX 76019-0407, USA.
R Soc Open Sci. 2024 Jul 31;11(7):240347. doi: 10.1098/rsos.240347. eCollection 2024 Jul.
This work presents a new framework for a competitive evolutionary game between monoclonal antibodies and signalling pathways in oesophageal cancer. The framework is based on a novel dynamical model that takes into account the dynamic progression of signalling pathways, resistance mechanisms and monoclonal antibody therapies. This game involves a scenario in which signalling pathways and monoclonal antibodies are the players competing against each other, where monoclonal antibodies use Brentuximab and Pembrolizumab dosages as strategies to counter the evolutionary resistance strategy implemented by the signalling pathways. Their interactions are described by the dynamical model, which serves as the game's playground. The analysis and computation of two game-theoretic strategies, Stackelberg and Nash equilibria, are conducted within this framework to ascertain the most favourable outcome for the patient. By comparing Stackelberg equilibria with Nash equilibria, numerical experiments show that the Stackelberg equilibria are superior for treating signalling pathways and are critical for the success of monoclonal antibodies in improving oesophageal cancer patient outcomes.
这项工作提出了一个关于食管癌中单克隆抗体与信号通路之间竞争性进化博弈的新框架。该框架基于一个新颖的动力学模型,该模型考虑了信号通路的动态进展、耐药机制和单克隆抗体疗法。此博弈涉及一种情景,其中信号通路和单克隆抗体作为相互竞争的参与者,单克隆抗体使用布伦妥昔单抗和帕博利珠单抗剂量作为策略来对抗信号通路实施的进化耐药策略。它们的相互作用由动力学模型描述,该模型充当博弈的场所。在这个框架内进行了两种博弈论策略(斯塔克尔伯格均衡和纳什均衡)的分析与计算,以确定对患者最有利的结果。通过将斯塔克尔伯格均衡与纳什均衡进行比较,数值实验表明,斯塔克尔伯格均衡在治疗信号通路方面更具优势,并且对于单克隆抗体改善食管癌患者预后的成功至关重要。