Patient-derived organoids as a predictive platform for drug sensitivity in bladder cancer

Area of Science:

• Oncology
• Biotechnology
• Genetics

Background:

• Bladder cancer (BC) displays significant heterogeneity, hindering standard treatment effectiveness.
• Personalized therapeutic strategies are crucial for improving patient outcomes in BC.

Purpose of the Study:

• To establish and characterize patient-derived organoids (PDOs) from bladder cancer specimens.
• To assess the utility of PDOs for modeling tumor heterogeneity and predicting drug responses.

Main Methods:

• 31 clinical bladder cancer specimens were used to generate patient-derived organoids (PDOs).
• PDOs underwent histological, molecular, and drug screening analyses.
• Responses to cisplatin, gemcitabine, and lapatinib were evaluated.

Main Results:

• An 80.65% success rate was achieved in establishing PDOs, which preserved tumor morphology and key molecular features.
• PDOs exhibited heterogeneous responses to standard-of-care agents and lapatinib.
• Lapatinib demonstrated dose-dependent enhancement of chemosensitivity, with synergistic effects observed in combination therapies.

Conclusions:

• Bladder cancer PDOs accurately recapitulate tumor heterogeneity and individual drug responses.
• PDOs serve as a valuable platform for preclinical drug evaluation and precision oncology.
• Combination therapies, such as lapatinib-enhanced chemotherapy, show potential for improved bladder cancer treatment.