Wang Jun, Zhang Le, Jing Chenyang, Ye Gang, Wu Hulin, Miao Hongyu, Wu Yukun, Zhou Xiaobo
College of Computer and Information Science, Southwest University, Chongqing 400715, China.
Theor Biol Med Model. 2013 Jun 21;10:41. doi: 10.1186/1742-4682-10-41.
Recently, melanoma has become the most malignant and commonly occurring skin cancer. Melanoma is not only the major source (75%) of deaths related to skin cancer, but also it is hard to be treated by the conventional drugs. Recent research indicated that angiogenesis is an important factor for tumor initiation, expansion, and response to therapy. Thus, we proposed a novel multi-scale agent-based computational model that integrates the angiogenesis into tumor growth to study the response of melanoma cancer under combined drug treatment.
Our multi-scale agent-based model can simulate the melanoma tumor growth with angiogenesis under combined drug treatment. The significant synergistic effects between drug Dox and drug Sunitinib demonstrated the clinical potential to interrupt the communication between melanoma cells and its related vasculatures. Also, the sensitivity analysis of the model revealed that diffusivity related to the micro-vasculatures around tumor tissues closely correlated with the spread, oscillation and destruction of the tumor.
Simulation results showed that the 3D model can represent key features of melanoma growth, angiogenesis, and its related micro-environment. The model can help cancer researchers understand the melanoma developmental mechanism. Drug synergism analysis suggested that interrupting the communications between melanoma cells and the related vasculatures can significantly increase the drug efficacy against tumor cells.
近年来，黑色素瘤已成为最具侵袭性且最为常见的皮肤癌。黑色素瘤不仅是皮肤癌相关死亡的主要来源（75%），而且常规药物对其治疗效果不佳。近期研究表明，血管生成是肿瘤起始、发展及对治疗反应的一个重要因素。因此，我们提出了一种基于多尺度智能体的计算模型，该模型将血管生成整合到肿瘤生长过程中，以研究黑色素瘤在联合药物治疗下的反应。
我们基于多尺度智能体的模型能够模拟联合药物治疗下伴有血管生成的黑色素瘤肿瘤生长。药物阿霉素（Dox）与药物舒尼替尼之间显著的协同效应表明了其在阻断黑色素瘤细胞与其相关脉管系统之间通讯方面的临床潜力。此外，该模型的敏感性分析显示，与肿瘤组织周围微血管相关的扩散率与肿瘤的扩散、振荡及破坏密切相关。
模拟结果表明，该三维模型能够呈现黑色素瘤生长、血管生成及其相关微环境的关键特征。该模型有助于癌症研究人员理解黑色素瘤的发展机制。药物协同分析表明，阻断黑色素瘤细胞与相关脉管系统之间的通讯能够显著提高药物对肿瘤细胞的疗效。
