Ribba Benjamin, Roller Andreas, Helms Hans-Joachim, Stern Martin, Bleul Conrad
Roche Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffman-La Roche Ltd, Basel, Switzerland.
Front Pharmacol. 2023 Mar 8;13:1058220. doi: 10.3389/fphar.2022.1058220. eCollection 2022.
To support further development of model-informed drug development approaches leveraging circulating tumor DNA (ctDNA), we performed an exploratory analysis of the relationships between treatment-induced changes to ctDNA levels, clinical response and tumor size dynamics in patients with cancer treated with checkpoint inhibitors and targeted therapies. This analysis highlights opportunities for pharmacometrics approaches such as for optimizing sampling design strategies. It also highlights challenges related to the nature of the data and associated variability overall emphasizing the importance of mechanistic modeling studies of the underlying biology of ctDNA processes such as shedding, release and clearance and their relationships with tumor size dynamic and treatment effects.
为支持利用循环肿瘤DNA（ctDNA）的模型 informed 药物开发方法的进一步发展，我们对接受检查点抑制剂和靶向治疗的癌症患者中ctDNA水平的治疗诱导变化、临床反应和肿瘤大小动态之间的关系进行了探索性分析。该分析突出了药物计量学方法的机会，例如优化采样设计策略。它还突出了与数据性质和相关变异性相关的挑战，总体上强调了对ctDNA过程（如脱落、释放和清除）的基础生物学及其与肿瘤大小动态和治疗效果的关系进行机制建模研究的重要性。
