A theoretical analysis of tumour containment.
A theoretical analysis of tumour containment.
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DOI：
10.1038/s41559-021-01428-w
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发表时间：
2021-06
影响因子：
16.8
通讯作者：
Noble R
中科院分区：
文献类型：
--
作者：
Viossat Y;Noble R
最近的研究表明，旨在遏制而不是消除的策略可以在体外、小鼠模型和临床中更有效地控制肿瘤负荷。这些结果与以下假设一致：通过利用药物敏感性和耐药性肿瘤细胞亚群之间的竞争性生态相互作用，可以预防或延迟对癌症治疗的耐药性的出现。然而，尽管已经提出了各种数学和计算模型来解释特定遏制策略的优越性，但这种癌症治疗的进化方法缺乏严格的理论基础。在这里，我们结合联合收割机广泛的数学分析和数值模拟，以建立一般条件下，遏制战略预计将更有效地控制肿瘤负荷比应用最大耐受剂量。我们表明，遏制可能大大优于更积极的治疗策略，即使阻力不会导致细胞健身成本。我们进一步提供了公式，用于预测在广泛的情况下，遏制战略的临床效益，并比较理论上最佳的治疗方案与更实用的协议的结果。我们的研究结果加强了进化知情癌症治疗的临床试验的基本原理，同时也澄清了遏制可能无法优于护理标准的条件。
Recent studies have shown that a strategy aiming for containment, not elimination, can control tumour burden more effectively in vitro, in mouse models and in the clinic. These outcomes are consistent with the hypothesis that emergence of resistance to cancer therapy may be prevented or delayed by exploiting competitive ecological interactions between drug-sensitive and drug-resistant tumour cell subpopulations. However, although various mathematical and computational models have been proposed to explain the superiority of particular containment strategies, this evolutionary approach to cancer therapy lacks a rigorous theoretical foundation. Here we combine extensive mathematical analysis and numerical simulations to establish general conditions under which a containment strategy is expected to control tumour burden more effectively than applying the maximum tolerated dose. We show that containment may substantially outperform more aggressive treatment strategies even if resistance incurs no cellular fitness cost. We further provide formulas for predicting the clinical benefits attributable to containment strategies in a wide range of scenarios and compare the outcomes of theoretically optimal treatments with those of more practical protocols. Our results strengthen the rationale for clinical trials of evolutionarily informed cancer therapy, while also clarifying conditions under which containment might fail to outperform standard of care.
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影响因子：
17.1
作者：
Enriquez-Navas PM;Kam Y;Das T;Hassan S;Silva A;Foroutan P;Ruiz E;Martinez G;Minton S;Gillies RJ;Gatenby RA
通讯作者：
Gatenby RA
影响因子：
9.8
作者：
Hansen E;Woods RJ;Read AF
通讯作者：
Read AF
影响因子：
1.8
作者：
Carrere, Cecile;Zidani, Hasnaa
通讯作者：
Zidani, Hasnaa
影响因子：
4.3
作者：
MARTIN, RB;FISHER, ME;TEO, KL
通讯作者：
TEO, KL
影响因子：
2
作者：
Monro, Helen C.;Gaffney, Eamonn A.
通讯作者：
Gaffney, Eamonn A.