ArticleClinical cancer research : an official journal of the American Association for Cancer Research2019
Multidrug Cancer Therapy in Metastatic Castrate-Resistant Prostate Cancer: An Evolution-Based Strategy.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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60 citing papers in PubMed, 117 citations in OpenAlex.
- The emerging role of prostate-specific membrane antigen-targeted radioligand therapy in metastatic hormone-sensitive prostate cancer.The oncologist · 2026Review
- Ensemble Optimal Control for Managing Drug Resistance in Cancer Therapies.Bulletin of mathematical biology · 2026Article
- Optimal control theory as a method for designing multidrug adaptive therapy regimens.NPJ systems biology and applications · 2026Article
- Directed Evolution Restored Castrate Sensitivity in a Patient With Castrate Resistant Metastatic Prostate Cancer.The Prostate · 2025Article
- Systems biology successes and areas for opportunity in prostate cancer.Endocrine-related cancer · 2025Review
- Bringing evolutionary cancer therapy to the clinic: a systems approach.NPJ systems biology and applications · 2025Review
- An integrative phenotype-structured partial differential equation model for the population dynamics of epithelial-mesenchymal transition.NPJ systems biology and applications · 2025Article
- Validating the predictions of mathematical models describing tumor growth and treatment response.ArXiv · 2025Article
- Stability of the Darwinian Dynamics: Effect of Intraspecific Competition and Human Intervention.Dynamic games and applications · 2025Article
- Adaptive Treatment of Metastatic Prostate Cancer Using Generative Artificial Intelligence.Clinical Medicine Insights. Oncology · 2025Review
- Cocrystal@protein-anchoring nanococktail for combinatorially treating multidrug-resistant cancer.Acta pharmaceutica Sinica. B · 2024Article
- Threshold-awareness in adaptive cancer therapy.PLoS computational biology · 2024Article
- The bone ecosystem facilitates multiple myeloma relapse and the evolution of heterogeneous drug resistant disease.Nature communications · 2024Article
- Deep reinforcement learning identifies personalized intermittent androgen deprivation therapy for prostate cancer.Briefings in bioinformatics · 2024Article
- A global sensitivity analysis of a mechanistic model of neoadjuvant chemotherapy for triple negative breast cancer constrained by in vitro and in vivo imaging data.Engineering with computers · 2024Article
- The effect of tumor composition on the success of adaptive therapy: The case of metastatic Castrate-Resistant Prostate Cancer.PloS one · 2024Article
- Article
- Treatment of evolving cancers will require dynamic decision support.Annals of oncology : official journal of the European Society for Medical Oncology · 2023Review
- Intermetastatic and Intrametastatic Heterogeneity Shapes Adaptive Therapy Cycling Dynamics.Cancer research · 2023Article
- Cellular barcoding tracks heterogeneous clones through selective pressures and phenotypic transitions.Trends in cancer · 2023Review
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6 authors at 2 institutions in 1 country.
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Abstract
purposeIntegration of evolutionary dynamics into systemic therapy for metastatic cancers can prolong tumor control compared with standard maximum tolerated dose (MTD) strategies. Prior investigations have focused on monotherapy, but many clinical cancer treatments combine two or more drugs. Optimizing the evolutionary dynamics in multidrug therapy is challenging because of the complex cellular interactions and the large parameter space of potential variations in drugs, doses, and treatment schedules. However, multidrug therapy also represents an opportunity to further improve outcomes using evolution-based strategies. EXPERIMENTAL
designWe examine evolution-based strategies for two-drug therapy and identify an approach that divides the treatment drugs into primary and secondary roles. The primary drug has the greatest efficacy and/or lowest toxicity. The secondary drug is applied solely to reduce the resistant population to the primary drug.
resultsSimulations from the mathematical model demonstrate that the primary-secondary approach increases time to progression (TTP) compared with conventional strategies in which drugs are administered without regard to evolutionary dynamics. We apply our model to an ongoing adaptive therapy clinical trial of evolution-based administration of abiraterone to treat metastatic castrate-resistant prostate cancer. Model simulations, parameterized with data from individual patients who progressed, demonstrate that strategic application of docetaxel during abiraterone therapy would have significantly increased their TTP.
conclusionsMathematical models can integrate evolutionary dynamics into multidrug cancer clinical trials. This has the potential to improve outcomes and to develop clinical trials in which these mathematical models are also used to estimate the mechanism(s) of treatment failure and explore alternative strategies to improve outcomes in future trials.
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