Prostate-specific antigen dynamics predict individual responses to intermittent androgen deprivation
Prostate-specific antigen dynamics predict individual responses to intermittent androgen deprivation
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DOI：
10.1038/s41467-020-15424-4
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发表时间：
2020-04-09
影响因子：
16.6
通讯作者：
Enderling, Heiko
中科院分区：
文献类型：
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作者：
Brady-Nicholls, Renee;Nagy, John D.;Enderling, Heiko
间歇性雄激素剥夺疗法（IADT）是一种有吸引力的治疗生物化学复发性前列腺癌（PCa），其中循环治疗可以减少累积剂量和限制毒性。我们模拟前列腺特异性抗原（PSA）动力学，在治疗过程中，PCa干细胞（PCaSC）的富集作为一种可能的耐药性进化机制。模拟PCaSC增殖模式与70例PCa患者的纵向血清PSA测量相关。在一项“留一”研究中，从每个治疗周期中学习动力学，模型模拟预测患者特异性耐药性演变的总体准确性为89%（敏感性=73%，特异性=91%）。先前的研究表明，在低和高体积转移性激素敏感的前列腺癌中，ADT同时治疗是有益的。基于第一个IADT周期反应动力学的模型模拟确定了将受益于同步多西他赛的患者，证明了由肿瘤内进化动力学的患者特异性数学模型指导的适应性临床试验的可行性和潜在价值。前列腺特异性抗原（PSA）是前列腺癌的生物标志物。在这里，作者开发了一个数学模型，其中PSA水平的纵向变化预测了前列腺癌患者对间歇性雄激素剥夺的反应。
Intermittent androgen deprivation therapy (IADT) is an attractive treatment for biochemically recurrent prostate cancer (PCa), whereby cycling treatment on and off can reduce cumulative dose and limit toxicities. We simulate prostate-specific antigen (PSA) dynamics, with enrichment of PCa stem-like cell (PCaSC) during treatment as a plausible mechanism of resistance evolution. Simulated PCaSC proliferation patterns correlate with longitudinal serum PSA measurements in 70 PCa patients. Learning dynamics from each treatment cycle in a leave-one-out study, model simulations predict patient-specific evolution of resistance with an overall accuracy of 89% (sensitivity=73%, specificity=91%). Previous studies have shown a benefit of concurrent therapies with ADT in both low- and high-volume metastatic hormone-sensitive PCa. Model simulations based on response dynamics from the first IADT cycle identify patients who would benefit from concurrent docetaxel, demonstrating the feasibility and potential value of adaptive clinical trials guided by patient-specific mathematical models of intratumoral evolutionary dynamics. Prostate specific antigen (PSA) is a biomarker for prostate cancer. Here, the authors develop a mathematical model where longitudinal changes in PSA levels predict responses to intermittent androgen deprivation in patients with prostate cancer.