Fig. 8: PIAS2b-dsRNAi has anticancer effect in vivo against human ATC in an orthotopic model. | Nature Communications

Fig. 8: PIAS2b-dsRNAi has anticancer effect in vivo against human ATC in an orthotopic model.

From: dsRNAi-mediated silencing of PIAS2beta specifically kills anaplastic carcinomas by mitotic catastrophe

Fig. 8

a–c Schematic cartoon of the design of the three preclinical trials (PCT1-2-3). NOD-SCID (PCT1) or NSG (PCT2 and PCT3) females were xeno-implanted orthotopically at the thyroid with patient-derived T-UC1 (PCT1) or T-UC7 (PCT2 and PCT3) cells (oPDX). Weeks later, intravenous treatment was started twice per week with ns-dsRNAi or PIAS2b-dsRNAi. Tumors were assessed weekly by luciferase intensity at IVIS device. At week 9, the endpoint was reached for PCT1 and PCT2. Primary purpose was Treatment. Secondary purpose for PCT2 was toxicity/resistance and treatment started after week 3. PCT3 was designed for Compassionate use and On-treatment started at week 7 with very advanced tumors, while Off-treatment was performed from week 10 to 11 (prolonged End-point). Arrows indicate treatment (color-coded similarly to animals): ns-dsRNAi (gray) or PIAS2b-dsRNAi (blue). d, f Lowess fitting curves performed for each treatment with all data included (black, ns-dsRNAi treatment; orange, PIAS2b dsRNAi treatment). Both datasets reach statistical significance at week 9 (p = 0.01) in PCT1 and PCT2, while no previous week presented significant differences. PCT3 datasets were p = 0.05 at week 10 (On-treatment) but lost significance at week 11 (Off-treatment). g Selected images from PCT1 of one participant in the ns-dsRNAi arm, and another from the PIAS2b-dsRNAi arm. h Increment signal at end-point compared to signal at start of treatment for each mouse in PCT1-2-3 were significantly reduced with treatment. Scale is bigger in NGS mice, due to enhanced signal. i Dissected oPDX fresh tumor volumes were significantly reduced in PIAS2b-dsRNAi treated mice. For d–f, h, and i ns-dsRNAi, n = 5 mice; PIAS2b-dsRNAi, n = 4–5 mice. d–f Two-sided two-way ANOVA with repeated measures, and fit spline/Lowess medium. For h, i (PCT1, PCT3) one-sided unpaired T-test, and (PCT2) one-sided Mann–Whitney. Indicated means ± SEM, and exact p value. ns not significant. Source data are provided as a Source Data file.

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