Dynamics of growth factor production in monolayers of cancer cells and evolution of resistance to anticancer therapies.
Dynamics of growth factor production in monolayers of cancer cells and evolution of resistance to anticancer therapies.
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DOI：
10.1111/eva.12092
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发表时间：
2013-12
影响因子：
4.1
通讯作者：
Archetti M
中科院分区：
文献类型：
--
作者：
Archetti M
肿瘤的异质性具有许多特征，包括产生生长因子，这些生长因子可以促进肿瘤的增殖，促进对细胞凋亡和免疫反应的抵抗。什么保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。虽然有人提出，针对生长因子的疗法对进化耐药是强有力的，但目前针对生长因子的疗法，如抗血管生成药物，从长远来看并不有效，因为耐药突变可能会进化并导致复发。我们使用进化博弈论来研究单层癌细胞产生生长因子的动力学，并了解针对生长因子的治疗的效果。这种动态取决于生长因子的生产成本、其扩散范围以及它为细胞带来的好处的类型。稳定的异质性是动力学的典型结果，而在某些条件下，非生产型细胞的纯粹平衡是可能的。这种纯粹的平衡可能是新的抗癌疗法的目标。相反，我们表明，目前的治疗方法只有在几乎完全消除增长因素并且几乎立即减少的情况下才能有效。
Tumor heterogeneity is well documented for many characters, including the production of growth factors, which improve tumor proliferation and promote resistance against apoptosis and against immune reaction. What maintains heterogeneity remains an open question that has implications for diagnosis and treatment. While it has been suggested that therapies targeting growth factors are robust against evolved resistance, current therapies against growth factors, like antiangiogenic drugs, are not effective in the long term, as resistant mutants can evolve and lead to relapse. We use evolutionary game theory to study the dynamics of the production of growth factors by monolayers of cancer cells and to understand the effect of therapies that target growth factors. The dynamics depend on the production cost of the growth factor, on its diffusion range and on the type of benefit it confers to the cells. Stable heterogeneity is a typical outcome of the dynamics, while a pure equilibrium of nonproducer cells is possible under certain conditions. Such pure equilibrium can be the goal of new anticancer therapies. We show that current therapies, instead, can be effective only if growth factors are almost completely eliminated and if the reduction is almost immediate.
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影响因子：
8.8
作者：
Archetti M
通讯作者：
Archetti M
DOI：
10.1073/pnas.0606053103
发表时间：
2006-09-05
影响因子：
11.1
作者：
Axelrod, Robert;Axelrod, David E.;Pienta, Kenneth J.
通讯作者：
Pienta, Kenneth J.
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：
Deutsch, A.
影响因子：
8.8
作者：
Ashley, D J
通讯作者：
Ashley, D J