Patient-derived organoids based on targeted biopsy of primary prostate cancer: development, identification, and drug screening.

OBJECTIVES

To develop patient-derived organoids (PDOs) using biopsied tissue of primary prostate cancer (PCa).

METHODS

Fresh tumour tissues of PCa were obtained from patients who underwent targeted biopsy in our centre for the culture of PDOs. Hematoxylin-Eosin (H & E) and immunohistochemical staining were used to determine the histology of the cultured PDOs, using the parental tumours as the reference. Whole exome sequencing (WES) was conducted to verify the genetic conservation of PDOs, using the parental tumours as the reference. Drug screening was carried out to test the feasibility of PDOs as preclinical models.

RESULTS

H & E and immunohistochemical staining indicated similar pathologic features between our developed PDOs and the parental tumours. WES also demonstrated similar somatic mutations, base substitutions and copy number variations between PDOs and the parental tumours. Drug screening results showed heterogeneity of the cultured PDOs to enzalutamide, docetaxel, and olaparib.

CONCLUSION

PDOs can be successfully developed based on targeted biopsy of primary PCa, which may be an optimal preclinical model to predict treatment response in the era of precision medicine.