Ribba B, You B, Tod M, Girard P, Tranchand B, Trillet-Lenoir V, Freyer G
Universite de Lyon, Lyon, France.
IET Syst Biol. 2009 May;3(3):180-90. doi: 10.1049/iet-syb.2008.0104.
The aim here was to explore the potential of pharmacokinetic (PK)/pharmacodynamic (PD) and physiopathological parameters in explaining the primary effects of an anti-cancer treatment that targets cells in a specific cell cycle phase. The authors applied a theoretical multi-scale disease model of tumour growth that integrates cancer processes at the cellular and tissue scales. The mathematical model at the cell level relies on a dynamic description of cell cycle regulation while the model at the tissue level is based on fluid mechanics considerations. Simulations show that the number of target cells oscillates as the tumour grows after a first cycle of chemotherapy. Both treatment effect and tumour growth processes drive these oscillations. Nonetheless, results indicate that parameters related to physiopathological processes may have greater relevance than classical drug-related parameters in determining the efficacy of a chemotherapy treatment protocol. Physiopathological parameters, in particular those related to cell cycle regulation, may be integrated in PK/PD models aimed at optimising the delivery of phase-specific cytotoxic treatments.
本文旨在探讨药代动力学(PK)/药效动力学(PD)以及生理病理参数在解释针对特定细胞周期阶段细胞的抗癌治疗的主要效果方面的潜力。作者应用了一种肿瘤生长的理论多尺度疾病模型,该模型整合了细胞和组织尺度上的癌症过程。细胞水平的数学模型依赖于细胞周期调控的动态描述,而组织水平的模型则基于流体力学考虑。模拟结果表明,在化疗的第一个周期后,随着肿瘤生长,靶细胞数量会发生振荡。治疗效果和肿瘤生长过程都会驱动这些振荡。尽管如此,结果表明,在确定化疗治疗方案的疗效方面,与生理病理过程相关的参数可能比经典的药物相关参数具有更大的相关性。生理病理参数,特别是那些与细胞周期调控相关的参数,可以整合到旨在优化特定阶段细胞毒性治疗给药的PK/PD模型中。