Current State and Critical Challenges in Prostate Cancer Organoid Culture.

Authors

Mariia Silkina, Maria Mastykina, Timur Kulagin, Margarita Beskhizhko, Alexandra Razumovskaya, Alina Shatsillo, Karina Klycheva, Nina Gorban, Oleg Karyakin, Vladimir Chaykov, Yana Gridneva, Boris Alekseev, Alexander Tonevitsky, Sergey Nikulin

Published in

Current medicinal chemistry. Nov 06, 2026. Epub Nov 06, 2026.

Abstract

Three-dimensional prostate cancer organoids represent a promising platform for modeling tumor biology and personalizing therapeutic strategies. However, unlike many other solid tumors, reproducing this pathology in vitro is challenging. Despite initial culture establishment rates reaching 70-90% in certain studies, most cultures undergo early growth arrest (typically within passages P1-P3 or the first 1-2 months), accompanied by a high risk of losing the target tumor clone. In the present work, we provide a critical analysis of the current state of 3D prostate cancer culture technologies and attempt to identify the fundamental reasons for the inefficiency of standard multicomponent media and traditional extracellular matrices. Based on the analysis of single-cell transcriptomic profiling data, we characterized the adaptive drift of organoid cellular composition toward basal and transient states. Furthermore, we substantiated the critical need to modernize approaches for confirming model relevance, particularly by analyzing in detail the limitations of traditional markers. As an effective solution, we propose the concept of integrating multiplex expression test systems based on accessible quantitative PCR platforms, utilizing the extensive arsenal of highly informative RNA biomarkers accumulated in clinical urologic oncology. We conclude that the transition from empirical condition selection to directed niche reconstruction based on single-cell analysis data combined with PCR verification will open new opportunities for the widespread implementation of organoid models in basic research and clinical practice.

PMID:
43023295
Bibliographic data and abstract were imported from PubMed on 13 Nov 2026.

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