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Deep reinforcement learning identifies personalized intermittent androgen deprivation therapy for prostate cancer

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单位: [1]School of Data Science, City University of Hong Kong, Hong Kong SAR, China. [2]Department of Thoracic Oncology, Tongji Hospital, Huazhong University of Science and Technology, 430030, Wuhan, China. [3]Department of Radiology, Tongji Hospital, Huazhong University of Science and Technology, 430030, Wuhan, China. [4]Department of Electrical and Computer Engineering and the Center for Statistics and Machine Learning, Princeton University, 08544, NJ, U.S.A. [5]Department of Integrated Mathematical Oncology and the Cancer Biology and Evolution Program, H. Lee Moffitt Cancer Center and Research Institute, 33612, FL, USA. [6]Musketeers Foundation Institute of Data Science and the Department of Pharmacology and Pharmacy, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
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关键词: Adaptive therapy Prostate cancer Personalized medicine Reinforcement learning

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The evolution of drug resistance leads to treatment failure and tumor progression. Intermittent androgen deprivation therapy (IADT) helps responsive cancer cells compete with resistant cancer cells in intratumoral competition. However, conventional IADT is population-based, ignoring the heterogeneity of patients and cancer. Additionally, existing IADT relies on pre-determined thresholds of prostate-specific antigen to pause and resume treatment, which is not optimized for individual patients. To address these challenges, we framed a data-driven method in two steps. First, we developed a time-varied, mixed-effect and generative Lotka-Volterra (tM-GLV) model to account for the heterogeneity of the evolution mechanism and the pharmacokinetics of two ADT drugs Cyproterone acetate and Leuprolide acetate for individual patients. Then, we proposed a reinforcement-learning-enabled individualized IADT framework, namely, I$^{2}$ADT, to learn the patient-specific tumor dynamics and derive the optimal drug administration policy. Experiments with clinical trial data demonstrated that the proposed I$^{2}$ADT can significantly prolong the time to progression of prostate cancer patients with reduced cumulative drug dosage. We further validated the efficacy of the proposed methods with a recent pilot clinical trial data. Moreover, the adaptability of I$^{2}$ADT makes it a promising tool for other cancers with the availability of clinical data, where treatment regimens might need to be individualized based on patient characteristics and disease dynamics. Our research elucidates the application of deep reinforcement learning to identify personalized adaptive cancer therapy.© The Author(s) 2024. Published by Oxford University Press.

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出版当年[2023]版:
大类 | 2 区 生物学
小类 | 1 区 生化研究方法 1 区 数学与计算生物学
最新[2025]版:
大类 | 2 区 生物学
小类 | 1 区 数学与计算生物学 2 区 生化研究方法
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第一作者单位: [1]School of Data Science, City University of Hong Kong, Hong Kong SAR, China.
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