Soboleva Arina, Kaznatcheev Artem, Cavill Rachel, Schneider Katharina, Staňková Kateřina
Institute for Health Systems Science, Faculty of Technology, Policy and Management, Delft University of Technology, Delft, The Netherlands.
Department of Mathematics and Department of Information and Computing Sciences, Utrecht University, Utrecht, The Netherlands.
PLoS One. 2025 Jan 9;20(1):e0310844. doi: 10.1371/journal.pone.0310844. eCollection 2025.
Mathematical modeling plays an important role in our understanding and targeting therapy resistance mechanisms in cancer. The polymorphic Gompertzian model, analyzed theoretically and numerically by Viossat and Noble to demonstrate the benefits of adaptive therapy in metastatic cancer, describes a heterogeneous cancer population consisting of therapy-sensitive and therapy-resistant cells. In this study, we demonstrate that the polymorphic Gompertzian model successfully captures trends in both in vitro and in vivo data on non-small cell lung cancer (NSCLC) dynamics under treatment. Additionally, for the in vivo data of tumor dynamics in patients undergoing treatment, we compare the goodness of fit of the polymorphic Gompertzian model to that of the classical oncologic models, which were previously identified as the models that fit this data best. We show that the polymorphic Gompertzian model can successfully capture the U-shape trend in tumor size during cancer relapse, which can not be fitted with the classical oncologic models. In general, the polymorphic Gompertzian model corresponds well to both in vitro and in vivo real-world data, suggesting it as a candidate for improving the efficacy of cancer therapy, for example, through evolutionary/adaptive therapies.
数学建模在我们理解癌症治疗耐药机制并将其作为治疗靶点方面发挥着重要作用。维奥萨特和诺布尔对多态性冈珀茨模型进行了理论和数值分析,以证明适应性疗法在转移性癌症中的益处,该模型描述了一个由治疗敏感细胞和治疗耐药细胞组成的异质性癌症群体。在本研究中,我们证明多态性冈珀茨模型成功捕捉了非小细胞肺癌(NSCLC)在治疗过程中的体外和体内动力学数据趋势。此外,对于接受治疗患者的肿瘤动力学体内数据,我们将多态性冈珀茨模型的拟合优度与经典肿瘤学模型的拟合优度进行了比较,经典肿瘤学模型此前被认为是最适合该数据的模型。我们表明,多态性冈珀茨模型能够成功捕捉癌症复发期间肿瘤大小的U形趋势,而经典肿瘤学模型无法拟合这一趋势。总体而言,多态性冈珀茨模型与体外和体内的实际数据都非常吻合,这表明它有潜力通过进化/适应性疗法等方式提高癌症治疗的疗效。