Ribba B, Saut O, Colin T, Bresch D, Grenier E, Boissel J P
Clinical Pharmacology Department, Institute for Theoretical Medicine, EA 3736, Faculty of Medicine R.T.H Laennec, University of Lyon 1, Paradin St., 69376 Lyon Cedex 08, France.
J Theor Biol. 2006 Dec 21;243(4):532-41. doi: 10.1016/j.jtbi.2006.07.013. Epub 2006 Jul 21.
With the aim of inhibiting cancer growth and reducing the risk of metastasis, pharmaceutical companies in the early 1990s developed anti-metastatic agents called inhibitors of metalloproteinases (MMPi). Despite the promising results obtained in pre-clinical studies, results of Phase III trials have been somewhat disappointing for late stage cancer patients. With the aim of mathematically investigating this therapeutic failure, we developed a mechanistically based model which integrates cell cycle regulation and macroscopic tumor dynamics. By simulating the model, we evaluated the efficacy of MMPi therapy. Simulation results predict the lack of efficacy of MMPi in advanced cancer patients. The theoretical model may aid in evaluating the efficacy of anti-metastatic therapies, thus benefiting the design of prospective clinical trials.
为了抑制癌症生长并降低转移风险，20世纪90年代初制药公司开发了一种名为金属蛋白酶抑制剂（MMPi）的抗转移药物。尽管临床前研究取得了令人鼓舞的结果，但III期试验结果对晚期癌症患者来说却有些令人失望。为了从数学角度研究这种治疗失败的原因，我们开发了一个基于机制的模型，该模型整合了细胞周期调控和宏观肿瘤动力学。通过模拟该模型，我们评估了MMPi疗法的疗效。模拟结果预测MMPi对晚期癌症患者缺乏疗效。该理论模型可能有助于评估抗转移疗法的疗效，从而有利于前瞻性临床试验的设计。
