Figure 5 from Precision Oncology and Systemic Targeted Therapy in Pseudomyxoma Peritonei
Authors: Martínez-Quintanilla Jordi , Cabot Débora , Sabia Doménico , Arqués Oriol , Vergés Jordi , Chicote Irene , Bijelic Lana , Cabellos Laia , Alcántara Anna M. , Ramos Isabel , Barrios Pedro , Crusellas Oriol , Palacio Lina M. , Cámara Juan A. , Barriuso Jorge , Jiménez Juan J. , Muñoz-Torres Pau , Nonell Lara , Flores Raquel , Médico Enzo , Guaglio Marcello , Ros Javier , Élez Elena , Tabernero Josep , Aziz Omer , Deraco Marcello , Palmer Héctor G. , Giovanna Chiorino , Francesco Mazzarotto , Manuela Gariboldi , Luca Varinelli , Tommaso Cavalleri , Bipasha Chakrabarty , Raghavendar Nagaraju , Patrick Caswell , Milly McAllister 
Published: September 2024

<p>BRAF inhibitor reduces tumor growth in an orthotopic <i>BRAF</i><sup>V600E</sup> PMP-PDX model. <i>BRAF</i><sup>V600E</sup> mutant PMP-PDX mucinous tumor tissue from PMP5.1 was implanted intraperitoneally in mice. Animals were scanned using microCT at day 3 and day 6 after tumor implantation. <b>A,</b> Representation of paired tumor volume of each mouse at day 3 and 6 after tumor implantation. Significant differences were assessed using Unpaired <i>t</i> test (****, <i>P</i> < 0.0001). <b>B–H,</b> Based on the microCT images, at day 6 animals were divided in four groups and treated with vehicle, intraperitoneal cetuximab (20 mg/kg), oral encorafenib (20 mg/kg), or doublet (<i>n</i> = 10–11/group). <b>B,</b> Representation of the FC in percentage of body weight the treated mice overtime. Mean ± SEM is shown. Significant differences were assessed using one-way ANOVA and Dunnett’s multiple comparisons tests compared to the vehicle group. Unpaired <i>t</i> test to assess significant differences in encorafenib and doublet group was used at the end of experiment. (**, <i>P</i> value < 0.01; ***, <i>P</i> value < 0.001; ****, <i>P</i> value < 0.0001). <b>C–F,</b> At day 37, animals were monitored with microCT and a representative animal of each group was euthanized. <b>C,</b> FC representation of the tumor volume from microCT images from representative mice from each group (<i>n</i> = 2–4). Mean ± SEM is shown. Significant differences were assessed using one-way ANOVA and Dunnett’s multiple comparisons tests compared to vehicle group (*, <i>P</i> value < 0.05). <b>D</b> and <b>E,</b> Axial, coronal, and sagittal microCT images (<b>D</b>) and tridimensional rendering of microCT studies (<b>E</b>) from a representative mouse from each group. <b>E,</b> Pallid blue mucinous tissue volume and pallid yellow bone structures/tissue are shown. <b>F,</b> Postmortem images of mice (top) and tumor lesions in the peritoneal cavity (bottom) are shown. <b>G</b> and <b>H,</b> Animals were euthanized when they reached the end point criteria of 50% of increase in body weight. <b>G,</b> Quantification of the weight increase (left) and the volume of mucinous tumor (right) isolated from the intra-abdominal cavity when mice reached the end point criteria. Mean ± SEM is shown. Significant differences were assessed using one-way ANOVA and Tukey’s multiple comparisons tests (**, <i>P</i> value < 0.01; ***, <i>P</i> value < 0.001; ****, <i>P</i> value < 0.0001). <b>H,</b> Survival curves from each group. Overall mice survival was evaluated by the Kaplan–Meier survival curve and log-rank test group (****, <i>P</i> value < 0.0001). PMP, Pseudomyxoma peritonei; PDX, Patient-derived xenografts.</p>