The rising mortality in lung cancer, as well as the constraints of the existing drugs, have made it a major research topic. DNA damage marks the early onset of cancer as it often results from vulnerabilities due to UV rays, oxidative stress, ionizing radiation, and various types of genotoxic attacks. p53 plays an unequivocal role in the DNA repair process and has an abiding presence at the crossroads of the pathways linking DNA damage and cancer. p53 also regulates autophagy in a dual manner based on its cellular localization. The plexus of autophagy regulated by p53 includes AMPK and BCL2, which are positive and negative regulators of prime autophagy inducer beclin1, respectively. Although autophagy is a quintessential process, its levels need to be monitored as uncontrolled autophagy may lead to cell death. The association of p53 and autophagic cell death is very vital as the former acts whenever any threat comes to DNA while the latter may play a role in getting rid of the culprit cell. Therefore, in this paper, we have formulated a seven-dimensional mathematical model connecting p53, DNA damage, and autophagy in lung cancer. We performed both local and global sensitivity analysis along with parameter recalibration analysis to understand the system dynamics. We hypothesized that, by the modulation of beclin1 level, the regulation of AMPK and BCL2 could be a possible strategy to mitigate the progression of lung cancer.

肺癌死亡率的上升以及现有药物的限制使其成为一个主要的研究课题。DNA 损伤标志着癌症的早期发作，因为它通常是由紫外线、氧化应激、电离辐射和各种类型的基因毒性攻击引起的脆弱性造成的。p53 在 DNA 修复过程中发挥着明确的作用，并且一直存在于连接 DNA 损伤和癌症的途径的十字路口。p53 还基于其细胞定位以双重方式调节自噬。受 p53 调控的自噬丛包括 AMPK 和 BCL2，它们分别是自噬诱导物 beclin1 的正负调节因子。尽管自噬是一个典型的过程，但需要监测其水平，因为不受控制的自噬可能导致细胞死亡。p53 与自噬细胞死亡的关联非常重要，因为当 DNA 受到任何威胁时，前者就会起作用，而后者可能会在清除罪魁祸首细胞方面发挥作用。因此，在本文中，我们建立了连接肺癌中 p53、DNA 损伤和自噬的七维数学模型。我们进行了局部和全局灵敏度分析以及参数重新校准分析，以了解系统动力学。我们假设，通过调节 beclin1 水平，调节 AMPK 和 BCL2 可能是减缓肺癌进展的一种可能策略。我们已经建立了一个连接肺癌中 p53、DNA 损伤和自噬的七维数学模型。我们进行了局部和全局灵敏度分析以及参数重新校准分析，以了解系统动力学。我们假设，通过调节 beclin1 水平，调节 AMPK 和 BCL2 可能是减缓肺癌进展的一种可能策略。我们已经建立了一个连接肺癌中 p53、DNA 损伤和自噬的七维数学模型。我们进行了局部和全局灵敏度分析以及参数重新校准分析，以了解系统动力学。我们假设，通过调节 beclin1 水平，调节 AMPK 和 BCL2 可能是减缓肺癌进展的一种可能策略。