Extended Data Fig. 10. Efficacy assessment of LLC0150 in prostate cancer organoids and xenografts.
a) Representative images of NSD2 IHC in a panel of patient-derived xenografts (PDXs). Scale bar:50 µm. b) Immunoblot of NSD2, AR targets, and histone marks in the LuCaP 23.1 PDX-derived organoid line treated with LLC0150, the NSD1/2 degrader. Total H3 is the loading control. c) Barplots showing relative viability of the PDX-derived organoid lines treated with two doses of LLC0150. In all lines, degradation of NSD1/2 reduces cell viability (n = 6 biological replicates; one-way ANOVA and Tukey’s test). Mean +/- SEM are shown. d) Growth curves (Cell-titer Glo) of two representative AR/NSD2-positive PDX-derived organoid lines treated with DMSO or LLC0150 (n = 6 biological replicates; one-way ANOVA and Tukey’s test). Mean +/- SEM are shown. e) Schematic overview of the LLC0150 intratumoral injection study in a VCaP xenograft model. f) Top: Representative NSD2 and KI67 IHC images in the vehicle and LLC0150-treated tumors. Loss of NSD2 correlates with a reduction in proliferating KI67-positive cells. Bottom: TUNEL assay in the vehicle and LLC0150-treated tumors reveal a high number of apoptotic (TUNEL-positive) cells in the drug-treated tumors.Vehicle, n = 3 tumors; LLC0150, n = 4 tumors. Scale bar: 50 µm. g) Immunoblot of noted proteins in matched tumor lysates from f. Total H3 is used as a loading control.