A new ecologically inspired paradigm in cancer treatment known as "adaptive therapy" capitalizes on competitive interactions between drug-sensitive and drug-resistant subclones. The goal of adaptive therapy is to maintain a controllable stable tumor burden by allowing a significant population of treatment-sensitive cells to survive. These, in turn, suppress proliferation of the less-fit resistant populations. However, there remain several open challenges in designing adaptive therapies, particularly in extending these therapeutic concepts to multiple treatments. We present a cancer treatment case study (metastatic castrate-resistant prostate cancer) as a point of departure to illustrate three novel concepts to aid the design of multidrug adaptive therapies. First, frequency-dependent "cycles" of tumor evolution can trap tumor evolution in a periodic, controllable loop. Second, the availability and selection of treatments may limit the evolutionary "absorbing region" reachable by the tumor. Third, the velocity of evolution significantly influences the optimal timing of drug sequences. These three conceptual advances provide a path forward for multidrug adaptive therapy. SIGNIFICANCE: Driving tumor evolution into periodic, repeatable treatment cycles provides a path forward for multidrug adaptive therapy.

中文翻译：

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迈向多药自适应疗法。

在癌症治疗中一种新的受生态启发的范例称为“自适应疗法”，它利用了对药物敏感和对药物耐药的亚克隆之间的竞争性相互作用。适应性治疗的目标是通过使大量对治疗敏感的细胞存活来维持可控的稳定肿瘤负荷。这些反过来又抑制了抗性较弱的人群的增殖。然而，在设计适应性疗法中，尤其是在将这些治疗概念扩展到多种疗法中，仍然存在一些开放的挑战。我们提出了一个癌症治疗案例研究（转移性去势抵抗性前列腺癌）作为出发点，以说明三个有助于多药适应性疗法设计的新颖概念。首先，频率相关的“周期” 肿瘤进化的过程可以将肿瘤进化陷于一个周期性的，可控制的循环中。其次，治疗方法的可用性和选择可能会限制肿瘤可达到的进化“吸收区”。第三，进化速度显着影响药物序列的最佳时机。这三项概念上的进展为多药适应性治疗提供了一条前进的道路。意义：将肿瘤发展为周期性，可重复的治疗周期，为多药适应性治疗提供了一条途径。这三项概念上的进展为多药适应性治疗提供了一条前进的道路。意义：将肿瘤发展为周期性，可重复的治疗周期，为多药适应性治疗提供了一条途径。这三项概念上的进展为多药适应性治疗提供了一条前进的道路。意义：将肿瘤发展为周期性，可重复的治疗周期，为多药适应性治疗提供了一条途径。