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Updated: Apr 9, 2026
Culture of Bladder Cancer Organoids as Precision Medicine Tools
Published on: December 28, 2021
Preclinical optimization of a broad-spectrum anti-bladder cancer tri-drug regimen via the Feedback System Control
Qi Liu1, Cheng Zhang2, Xianting Ding3
1School of Life Science and Technology, State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin, Heilongjiang 150001, China, and Department of Anatomy and Cell Biology, University of Iowa, Carver College of Medicine, Iowa City, IA 52242, USA.
Abstract:
Therapeutic outcomes of combination chemotherapy have not significantly advanced during the past decades. This has been attributed to the formidable challenges of optimizing drug combinations. Testing a matrix of all possible combinations of doses and agents in a single cell line is unfeasible due to the virtually infinite number of possibilities. We utilized the Feedback System Control (FSC) platform, a phenotype oriented approach to test 100 options among 15,625 possible combinations in four rounds of assaying to identify an optimal tri-drug combination in eight distinct chemoresistant bladder cancer cell lines. This combination killed between 82.86% and 99.52% of BCa cells, but only 47.47% of the immortalized benign bladder epithelial cells. Preclinical in vivo verification revealed its markedly enhanced anti-tumor efficacy as compared to its bi- or mono-drug components in cell line-derived tumor xenografts. The collective response of these pathways to component drugs was both cell type- and drug type specific. However, the entire spectrum of pathways triggered by the tri-drug regimen was similar in all four cancer cell lines, explaining its broad spectrum killing of BCa lines, which did not occur with its component drugs. Our findings here suggest that the FSC platform holds promise for optimization of anti-cancer combination chemotherapy.
Insights
Optimizing cancer drug combinations is challenging. A Feedback System Control (FSC) platform identified a potent tri-drug regimen for bladder cancer (BCa) with significant anti-tumor efficacy in preclinical models.
Area of Science:
- Oncology
- Pharmacology
- Biotechnology
Background:
- Combination chemotherapy outcomes have stagnated due to challenges in optimizing drug combinations.
- Testing all possible drug combinations is infeasible due to the vast number of possibilities.
Purpose of the Study:
- To utilize the Feedback System Control (FSC) platform to identify an optimal tri-drug combination for chemoresistant bladder cancer.
- To evaluate the efficacy and specificity of the identified combination in vitro and in vivo.
Main Methods:
- The FSC platform tested 100 combinations out of 15,625 possibilities across eight chemoresistant bladder cancer cell lines.
- Phenotype-oriented approach involving four rounds of assays.
- In vivo verification using cell line-derived tumor xenografts.
Main Results:
- An optimal tri-drug combination demonstrated high efficacy, killing 82.86%-99.52% of bladder cancer cells while sparing benign cells (47.47%).
- The combination showed enhanced anti-tumor efficacy in vivo compared to mono- or bi-drug treatments.
- A similar spectrum of triggered pathways across cancer cell lines explained the broad-spectrum efficacy.
Conclusions:
- The FSC platform is a promising tool for optimizing anti-cancer combination chemotherapy.
- The identified tri-drug regimen offers a potential strategy for treating chemoresistant bladder cancer.
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