ArticleThe Prostate2025
Directed Evolution Restored Castrate Sensitivity in a Patient With Castrate Resistant Metastatic Prostate Cancer.
Article in The Prostate, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
2 citing papers in PubMed.
- Tumor‑immune spatiotemporal co‑evolution: A new paradigm for understanding and overcoming therapy resistance in metastatic castration‑resistant prostate cancer (Review).International journal of molecular medicine · 2026Review
- Multidimensional tumor heterogeneity and its role in therapeutic resistance.Frontiers in immunology · 2026Review
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
objectiveFor centuries, humans have used directed evolution to promote desired traits in domesticated animals. We hypothesized similar strategies may be employed to steer castrate resistant prostate cancer cells to a castrate sensitive phenotype allowing resumption of Androgen Deprivation therapy (ADT) and prolonging survival.
methodsOur interdisciplinary team investigated directed evolution to restore castrate sensitivity in a patient with metastatic castrate resistant prostate cancer who could not tolerate available therapeutic agents for castrate resistant disease. Guided by an evolutionary mathematical model and using the PSA/testosterone ratio as a biomarker for intra-tumoral population dynamics, we applied a sequence of testosterone injections as evolutionary selection forces to suppress resistant androgen receptor-upregulated clones and promote proliferation of ADT-responsive clones.
resultsWhen the PSA/testosterone ratio indicated successful transition to dominant castrate sensitive population, reinstitution of adaptive dosing of ADT has resulted in three stable cycles.
conclusionThis case suggests that evolution-informed strategies using population-based biomarkers to manipulate intra-tumoral evolution can restore castrate sensitivity in select patients.
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