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

Yitao Lu, Qian Chu, Zhen Li, Mengdi Wang, Robert Gatenby, Qingpeng Zhang

Briefings in bioinformatics 2024 Jan 22

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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.

Citation

Yitao Lu, Qian Chu, Zhen Li, Mengdi Wang, Robert Gatenby, Qingpeng Zhang. Deep reinforcement learning identifies personalized intermittent androgen deprivation therapy for prostate cancer. Briefings in bioinformatics. 2024 Jan 22;25(2)