Conclusions
The results suggest that treatment of castrate-resistant prostate cancer by imipridones may not be substantially affected by neuroendocrine differentiation as a therapy-resistance mechanism. The results support further testing of imipridones across subtypes of androgen-sensitive and castrate-resistant prostate cancer.
Methods
Inducible SOX2 or BRN2 systems were cloned into human PCa cell lines LNCaP and DU145. Inducible cell lines were characterized based on protein expression, morphology, and migration. The sensitivity of the inducible cell lines to imipridone therapy was determined by viability, cell growth, or clonogenic assays.
Results
Slight protection from ONC201 or ONC206 with SOX2 and BRN2 overexpression was observed in the inducible LNCaP cells but not in the DU145 cells. At 2 months, there was an apparent increase in CLpP expression in LNCaP SOX2-overexpressing cells, though this did not confer enhanced sensitivity to ONC201. DU145 SOX2-overexpressing cells had a significantly reduced ONC201 sensitivity than DU145 control cells. Conclusions: The results suggest that treatment of castrate-resistant prostate cancer by imipridones may not be substantially affected by neuroendocrine differentiation as a therapy-resistance mechanism. The results support further testing of imipridones across subtypes of androgen-sensitive and castrate-resistant prostate cancer.