Evolutionary game theory of growth factor production: implications for tumour heterogeneity and resistance to therapies.
Evolutionary game theory of growth factor production: implications for tumour heterogeneity and resistance to therapies.
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DOI：
10.1038/bjc.2013.336
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发表时间：
2013-08-20
影响因子：
8.8
通讯作者：
Archetti M
中科院分区：
文献类型：
--
作者：
Archetti M
肿瘤异质性有许多特征，包括生长因子的产生，这是癌症的标志之一。是什么维持了异质性仍然是一个悬而未决的问题，对诊断和治疗有影响，因为靶向生长因子的药物容易出现耐药性。我使用进化博弈论来模拟癌细胞之间的集体相互作用，分析生长因子产生的动态以及减少其数量的治疗效果。五种类型的动力学是可能的，包括生产细胞和非生产细胞的共存，这取决于生长因子的生产成本、其扩散范围以及其赋予细胞的益处的协同程度。靶向生长因子的平衡模拟疗法的扰动在长期内有效地减少生长因子的量，只有当减少是极其有效和立即的。肿瘤内的集体相互作用可以维持生长因子产生的异质性，并解释了为什么抗血管生成药物和RNA干扰等减少可用生长因子量的疗法在短期内有效，但往往导致复发。进化稳定的治疗方法的替代策略进行了讨论。
Tumour heterogeneity is documented for many characters, including the production of growth factors, one of the hallmarks of cancer. What maintains heterogeneity remains an open question that has implications for diagnosis and treatment, as drugs that target growth factors are susceptible to the evolution of resistance. I use evolutionary game theory to model collective interactions between cancer cells, to analyse the dynamics of the production of growth factors and the effect of therapies that reduce their amount. Five types of dynamics are possible, including the coexistence of producer and non-producer cells, depending on the production cost of the growth factor, on its diffusion range and on the degree of synergy of the benefit it confers to the cells. Perturbations of the equilibrium mimicking therapies that target growth factors are effective in reducing the amount of growth factor in the long term only if the reduction is extremely efficient and immediate. Collective interactions within the tumour can maintain heterogeneity for the production of growth factors and explain why therapies like anti-angiogenic drugs and RNA interference that reduce the amount of available growth factors are effective in the short term but often lead to relapse. Alternative strategies for evolutionarily stable treatments are discussed.
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影响因子：
3.7
作者：
Iwasa Y;Michor F
通讯作者：
Michor F
影响因子：
64.8
作者：
Greaves, Mel;Maley, Carlo C.
通讯作者：
Maley, Carlo C.
DOI：
10.1073/pnas.0606053103
发表时间：
2006-09-05
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
4.1
作者：
Aktipis CA;Nesse RM
通讯作者：
Nesse RM
影响因子：
8.5
作者：
Basanta, D.;Simon, M.;Deutsch, A.
通讯作者：
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