ArticlePLoS computational biology2013
Systems modeling of anti-apoptotic pathways in prostate cancer: psychological stress triggers a synergism pattern switch in drug combination therapy.
Article in PLoS computational biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- The Impact of Chronic Stress on Treatment Outcomes of Cancer Patients with Divergent Survival Rates: A Systematic Review.International journal of molecular sciences · 2026Pooled it
- Integrating multi-omics data for next-generation cancer research and precision medicine.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Current Advancements in Untargeted Metabolomics Analysis and Testing Driven by Machine Learning: Prospects for Artificial Intelligence in Patient-Centric Healthcare Transformation.Applied biochemistry and biotechnology · 2026Review
- Mammalian synthetic gene circuits for biopharmaceutical development & manufacture.NPJ systems biology and applications · 2025Review
- Multiscale mathematical model-informed reinforcement learning optimizes combination treatment scheduling in glioblastoma evolution.Science advances · 2025Article
- A comprehensive review of computational cell cycle models in guiding cancer treatment strategies.NPJ systems biology and applications · 2024Review
- HormoNet: a deep learning approach for hormone-drug interaction prediction.BMC bioinformatics · 2024Article
- Systems Pharmacodynamic Model of Combined Gemcitabine and Trabectedin in Pancreatic Cancer Cells. Part I: Effects on Signal Transduction Pathways Related to Tumor GrowthJournal of pharmaceutical sciences · 2024Article
- Untargeted metabolomic analysis of thoracic blood from badgers indicate changes linked to infection with bovine tuberculosis (Mycobacterium bovis): a pilot study.Metabolomics : Official journal of the Metabolomic Society · 2022Article
- Predicting Anticancer Drug Resistance Mediated by Mutations.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Inferring microenvironmental regulation of gene expression from single-cell RNA sequencing data using scMLnet with an application to COVID-19.Briefings in bioinformatics · 2021Article
- βThe Prostate · 2020Article
- Differential regulatory network-based quantification and prioritization of key genes underlying cancer drug resistance based on time-course RNA-seq data.PLoS computational biology · 2019Article
- ADRB2-Targeting Therapies for Prostate Cancer.Cancers · 2019Review
- Mathematical modeling and computational prediction of cancer drug resistance.Briefings in bioinformatics · 2018Review
- Chi3l3: a potential key orchestrator of eosinophil recruitment in meningitis induced by Angiostrongylus cantonensis.Journal of neuroinflammation · 2018Article
- HIDEEP: a systems approach to predict hormone impacts on drug efficacy based on effect paths.Scientific reports · 2017Article
- Article
- Brefeldin A enhances docetaxel-induced growth inhibition and apoptosis in prostate cancer cells in monolayer and 3D cultures.Bioorganic & medicinal chemistry letters · 2017Article
- Predicting the impact of combined therapies on myeloma cell growth using a hybrid multi-scale agent-based model.Oncotarget · 2017Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Prostate cancer patients often have increased levels of psychological stress or anxiety, but the molecular mechanisms underlying the interaction between psychological stress and prostate cancer as well as therapy resistance have been rarely studied and remain poorly understood. Recent reports show that stress inhibits apoptosis in prostate cancer cells via epinephrine/beta2 adrenergic receptor/PKA/BAD pathway. In this study, we used experimental data on the signaling pathways that control BAD phosphorylation to build a dynamic network model of apoptosis regulation in prostate cancer cells. We then compared the predictive power of two different models with or without the role of Mcl-1, which justified the role of Mcl-1 stabilization in anti-apoptotic effects of emotional stress. Based on the selected model, we examined and quantitatively evaluated the induction of apoptosis by drug combination therapies. We predicted that the combination of PI3K inhibitor LY294002 and inhibition of BAD phosphorylation at S112 would produce the best synergistic effect among 8 interventions examined. Experimental validation confirmed the effectiveness of our predictive model. Moreover, we found that epinephrine signaling changes the synergism pattern and decreases efficacy of combination therapy. The molecular mechanisms responsible for therapeutic resistance and the switch in synergism were explored by analyzing a network model of signaling pathways affected by psychological stress. These results provide insights into the mechanisms of psychological stress signaling in therapy-resistant cancer, and indicate the potential benefit of reducing psychological stress in designing more effective therapies for prostate cancer patients.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.