Fig. 6: Noncanonical AR target expression in ENZ-R CRPC patient samples and therapeutic targeting of noncanonical AR activity in organoids and PDXs.

Representative images for HE staining and IHC of AR, CXXC5, and ID1 in hormone naive (n = 24), CRPC (n = 16), and ENZ-resistant (n = 13) PCa patient specimens (scale bar, 50 μm) (a) and quantification of IHC (b). Data are represented as means ± s.d. Statistical significance was determined by unpaired two-tailed Student’s t tests. c Western blot analysis of AR, CXXC5, TET2, ID1, PFN2, and ID3 in CRPC and ENZ-resistant PCa PDXs (three tumors for each PDX). d, e Organoids derived from CRPC and ENZ-resistant PDX tumors were treated with the indicated inhibitors for 10 days. Representative images (scale bar, 100 μm) were taken (d) and cell viability was determined (e). Data shown as ±s.d., (n = 5 replicates/group). Statistical significance was determined by unpaired two-tailed Student’s t tests. f–h Effect of the indicated inhibitors on ENZ-resistant PDX tumor volume and weight; Data shown as ±s.d., (n = 8 replicates/group). Statistical significance was determined by two-way ANOVA for tumor volume and by unpaired two-tailed Student’s t tests for tumor weight.