Abstract We formulated a mechanistic model for the cancer-immune system associated with therapy. In this model, cancer is divided into two types: cancer that is sensitive to treatment (CST) and cancer that gradually acquires resistance to therapeutic agents (CRT). Cancer activates various mechanisms to evade the actions of therapeutic agents, including chemotherapy or targeted therapy. A positive response is observed at the early stage of treatment when cancer therapy is administered through subcutaneous or intravenous injection. However, over time, cancer acquires resistance against the treatment and begins to show rapid growth. Previous models have suggested strategies that can effectively suppress cancer by determining an appropriate dosing regimen but are limited in that cancer inhibition depends only on the dose amount and regimen. In contrast to a model in which there is a steady decline in cancer due to continuous-infusion therapy, the proposed model incorporates the fact that cancer cells may grow despite successive therapy administration, owing to the transition from CST to CRT. This consideration indicates that cancer suppression can be determined by the delay of therapy delivery to the site of action and the transition time. The delay of therapy and the transition time thus determine the period of cancer growth and the increase or decrease in cancer cell growth, respectively. This model was then used to the ratio of CST to CRT and to explore the therapy infusion rate under constant and periodic conditions in association with a pharmacokinetic model.

中文翻译：

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考虑对治疗剂的获得性耐药性的阶段特异性癌症免疫模型

摘要 我们为与治疗相关的癌症免疫系统制定了一个机制模型。在该模型中，癌症分为两种类型：对治疗敏感的癌症 (CST) 和对治疗剂逐渐产生耐药性的癌症 (CRT)。癌症会激活各种机制来逃避治疗剂的作用，包括化疗或靶向治疗。当通过皮下或静脉注射进行癌症治疗时，在治疗的早期阶段观察到阳性反应。然而，随着时间的推移，癌症对治疗产生抵抗力并开始快速增长。以前的模型提出了通过确定适当的给药方案可以有效抑制癌症的策略，但其局限性在于癌症抑制仅取决于剂量和方案。与因连续输注治疗而导致癌症稳步下降的模型相比，所提出的模型包含了这样一个事实，即由于从 CST 到 CRT 的过渡，尽管连续进行治疗，癌细胞仍可能生长。这种考虑表明癌症抑制可以通过治疗递送到作用部位的延迟和过渡时间来确定。因此，治疗的延迟和过渡时间分别决定了癌症生长的时期和癌细胞生长的增加或减少。然后将该模型用于 CST 与 CRT 的比率，并结合药代动力学模型探索恒定和周期性条件下的治疗输注速率。由于从 CST 到 CRT 的过渡，所提出的模型包含了这样一个事实，即尽管进行了连续治疗，癌细胞仍可能会生长。这种考虑表明癌症抑制可以通过治疗递送到作用部位的延迟和过渡时间来确定。因此，治疗的延迟和过渡时间分别决定了癌症生长的时期和癌细胞生长的增加或减少。然后将该模型用于 CST 与 CRT 的比率，并结合药代动力学模型探索恒定和周期性条件下的治疗输注速率。由于从 CST 到 CRT 的过渡，所提出的模型包含了这样一个事实，即尽管进行了连续治疗，癌细胞仍可能会生长。这种考虑表明癌症抑制可以通过治疗递送到作用部位的延迟和过渡时间来确定。因此，治疗的延迟和过渡时间分别决定了癌症生长的时期和癌细胞生长的增加或减少。然后将该模型用于 CST 与 CRT 的比率，并结合药代动力学模型探索恒定和周期性条件下的治疗输注速率。这种考虑表明癌症抑制可以通过治疗递送到作用部位的延迟和过渡时间来确定。因此，治疗的延迟和过渡时间分别决定了癌症生长的时期和癌细胞生长的增加或减少。然后将该模型用于 CST 与 CRT 的比率，并结合药代动力学模型探索恒定和周期性条件下的治疗输注速率。这种考虑表明癌症抑制可以通过治疗递送到作用部位的延迟和过渡时间来确定。因此，治疗的延迟和过渡时间分别决定了癌症生长的时期和癌细胞生长的增加或减少。然后将该模型用于 CST 与 CRT 的比率，并结合药代动力学模型探索恒定和周期性条件下的治疗输注速率。