G5 Article dissertation
Exploring bladder cancer heterogeneity: towards new stratification approaches with patient-derived cells and steroid profiling; 
Authors: Kettunen, Kimmo
Publishing place: Turku
Publication year: 2026
Series title: Annales Universitatis Turkuensis D
Number in series: 1991
ISBN: 978-952-02-0788-5
eISBN: 978-952-02-0789-2
ISSN: 0355-9483
eISSN: 2343-3213
Publication's open availability at the time of reporting: Open Access
Publication channel's open availability : Open Access publication channel
Web address : https://urn.fi/URN:ISBN:978-952-02-0789-2
Background: Bladder cancer is a diverse disease with varying tumor types and treatment responses. Current therapies help only some patients, and treatment decisions are often made without personalized information. Bladder cancer is also much more common in men than in women, raising questions about the role of hormones. Aims: This doctoral study aimed to improve personalized treatment for bladder cancer patients by (1) evaluating whether patient-derived cell cultures can capture patient-specific ex vivo drug response patterns, and (2) analyzing sex hormone levels in bladder tumors and healthy tissues to understand their role in the disease. Methods: Bladder tumor cells were cultured from patient samples using conditional reprogramming, a feeder cell- and ROCK inhibitor-based method for propagating primary epithelial cells. These cultures were screened with multiple drugs. Steroid hormone levels were measured from tumors, healthy tissue, and blood using mass spectrometry, and gene expression was analyzed. Results: Patient-derived cells showed variable in vitro responses to multiple cancer drugs, suggesting that functional testing may reveal patient-specific ex vivo differences in drug sensitivity. However, not all cultures maintained cancer-specific features. Hormone profiling revealed extremely low androgen levels in tumors. Most tumors had hormone levels similar to castrated tissue, and androgen-blocking drugs showed limited cytotoxicity in the tested cultures. Conclusions: Patient-derived cultures may provide exploratory functional information on patient-specific ex vivo drug sensitivity and resistance, but prospective validation against matched clinical treatment outcomes is required before these responses can be interpreted as predictors of treatment benefit. Muscle-invasive bladder tumors have a markedly androgen-poor tissue environment, potentially limiting the efficacy of hormonal or anti-androgen-based therapies.