Development of patient‑derived tumor organoids and a drug testing model for renal cell carcinoma

Area of Science:

• Oncology
• Translational Medicine
• Biotechnology

Background:

• Effective therapeutic selection is crucial for improving survival in renal cell carcinoma (RCC) patients.
• Current treatment strategies often lack personalized efficacy, necessitating novel drug testing approaches.

Purpose of the Study:

• To develop an ex vivo drug testing assay utilizing patient-derived tumor organoids (TOs) for renal cell carcinoma.
• To evaluate the histopathological and molecular fidelity of these TOs.
• To assess the differential response of RCC TOs to standard tyrosine kinase inhibitors.

Main Methods:

• Surgical tumor specimens from 20 RCC patients were used to establish ex vivo tumor organoid (TO) cultures.
• Histological staining and whole-exome sequencing (WES) were employed to characterize TOs.
• Cell viability assays determined the efficacy of tyrosine kinase inhibitors (sunitinib, pazopanib, cabozantinib, axitinib, sorafenib) on RCC TOs.

Main Results:

• Tumor organoids successfully recapitulated the histological features of primary RCC tumors.
• Whole-exome sequencing demonstrated high genetic concordance between primary tumors and their corresponding TOs.
• RCC TOs exhibited differential responses to various tyrosine kinase inhibitors, indicating varied drug sensitivity.

Conclusions:

• A prototype ex vivo drug testing assay using patient-derived RCC tumor organoids was successfully developed.
• This novel approach shows potential for personalized cancer treatment by predicting drug responses.
• Further clinical validation is required to confirm the predictive value of this assay in patient care.