Extended Data Fig. 10: Combined in vivo treatment with AU-15330 and enzalutamide causes tumor regression in PCa xenografts without toxic effects on other organs.
From: Targeting SWI/SNF ATPases in enhancer-addicted prostate cancer

(a) Schematic outlining the AU-15330 in vivo efficacy study using the VCaP-CRPC xenograft model. VCaP cells were subcutaneously grafted in immunocompromised mice that were castrated after 2 weeks of tumor growth to induce disease regression. This was eventually followed by tumor re-growth in the androgen-depleted conditions, generating the aggressive, castration-resistant tumors. (b) Individual tumors and weights from vehicle, enzalutamide, AU-15330, and AU-15330+enzalutamide groups from VCaP-CRPC study (two-sided t-test). Data are presented as mean+/−SEM (vehicle: n = 18, enzalutamide: n = 20, AU-15330: n = 18, AU-15330+enzalutamide: n = 16). For all box plots, the center shows median, box marks quartiles 1–3, and whiskers span the range. (c) Immunoblots of direct AU-15330 targets (upper) and oncogenic transcription factors (bottom) from VCaP-CRPC xenografts (n = 4 tumors/arm) after 5 days of in vivo treatment. Vinculin is the loading control probed on a representative immunoblot. (d) Representative immunohistochemistry images from the VCaP-CRPC xenograft study (n = 2 tumors/arm) for SMARCA2 and SMARCA4. (e) Box plot of the percent of cells with positive Ki-67 staining. Two-sided t-test shows significant differences between vehicle vs. enzalutamide, AU-15330, or AU-15330+enzalutamide groups. Data are presented as mean +/− SEM (n = 4, biological replicates). For all box plots, the center shows median, box marks quartiles 1–3, and whiskers span the range. (f) Percent body weight measurement showing the effect of vehicle, enzalutamide, AU-15330, and combination of AU-15330 and enzalutamide throughout the treatment period (two-sided t-test). Data are presented as mean +/− SEM (vehicle: n = 9, enzalutamide: n = 10, AU-15330: n = 9, AU-15330 + enzalutamide: n = 8). (g) H&E staining was carried out to examine the effect of AU-15330 in vivo using colon, spleen, liver, and kidney sections after necropsy. Representative images of H&E staining are shown. (h) Immunohistochemistry staining of SMARCA4/BRG1 was carried out using liver and kidney sections after necropsy to show on-target efficacy of AU-15330 in vivo.