论文标题
自适应疗法中的开放问题的调查:桥接数学和临床翻译
A survey of open questions in adaptive therapy: bridging mathematics and clinical translation
论文作者
论文摘要
自适应疗法是一种动态癌症治疗方案,可更新(或“适应”)治疗决策,以期预期不断发展的肿瘤动态。这个广泛的术语涵盖了许多可能的动态治疗方案,该方案的特定剂量调节或剂量时间。自适应疗法维持高水平的肿瘤负担,以使对治疗敏感的亚群的竞争抑制对治疗的亚群体受益。这种基于进化的癌症治疗方法已纳入了几项正在进行的或计划的临床试验,包括治疗转移性castrate抗性前列腺癌,卵巢癌和BRAF-突变药物黑色素瘤。在过去的几十年中,适应性疗法的实验和临床研究与数学和计算建模协同发展。在这项工作中,我们讨论了癌症自适应疗法数学建模中的11个开放性问题。这些问题分为三个部分:1)自适应治疗的数学模型的必要组成部分2)剂量方案的设计和验证,以及3)临床翻译中的挑战和机会。
Adaptive therapy is a dynamic cancer treatment protocol that updates (or "adapts") treatment decisions in anticipation of evolving tumor dynamics. This broad term encompasses many possible dynamic treatment protocols of patient-specific dose modulation or dose timing. Adaptive therapy maintains high levels of tumor burden to benefit from the competitive suppression of treatment-sensitive subpopulations on treatment-resistant subpopulations. This evolution-based approach to cancer treatment has been integrated into several ongoing or planned clinical trials, including treatment of metastatic castrate resistant prostate cancer, ovarian cancer, and BRAF-mutant melanoma. In the previous few decades, experimental and clinical investigation of adaptive therapy has progressed synergistically with mathematical and computational modeling. In this work, we discuss 11 open questions in cancer adaptive therapy mathematical modeling. The questions are split into three sections: 1) the necessary components of mathematical models of adaptive therapy 2) design and validation of dosing protocols, and 3) challenges and opportunities in clinical translation.