Journal: bioRxiv

Article Title: Fibroblast-derived Collagen VI shapes the structure and function of the tumor-immune microenvironment in clear cell renal cell carcinoma

doi: 10.64898/2026.03.19.712351

Figure Lengend Snippet: ( A ) Survival analysis for high or low expression of COL6A1 and COL6A2 in the CheckMate 025 study cohort of Nivolumab (anti-PD-1) or everolimus (mTOR inhibitor) treated patients . Graphs show Kaplan-Meier plots and Log-rank (Mantel-Cox) tests. (B-D) Analysis of COL6 deposition in CDMs treated with cabozantinib (Cabo.), sunitinib (Suni.), temsirolimus (Temsi.), or DMSO (Ctrl.) treated TK173 cells. (B) Dot plot depicting relative median fluorescence intensities (MFI) of COL6 in CDMs of respectively treated cells in the screening experiment (N=10 regions of interest, one-way ANOVA with Tukey’s multiple comparison test). (C) Dot plot depicting mean relative MFI of COL6 in CDMs of respectively treated TK173 cells (dots indicate mean of N=4 independent experiments, unpaired t test). (D) IF images stained for FN (green) and COL6 (violet) of synthesized CDMs of TK173 cells treated with the indicated drugs. (E) Schematic description of RNA sequencing analysis of cabozantinib or DMSO control-treated TK173 fibroblasts and acute organotypic slice cultures (OTSCs) of ccRCCs (Created in BioRender. Schell, C. (2026) https://BioRender.com/x5sqb3y ). (F&G) Volcano plot of differential gene expression analysis of matrisome genes in cabozantinib-treated TK173 cells and ccRCC OTSCs. The inserts depict a volcano plot of all genes. Red dots indicate significantly regulated genes with adjusted p<0.01 and log 2 fold change (FC) > |1|). (H) Heatmap analysis of significantly regulated matrisome genes in cabozantinib-treated TK173 cells and ccRCC OTSCs (genes with adjusted p<0.0001 and fold change > |2| are depicted for TK173 cells or with adjusted p<0.01 and fold change > |1.5| for OTSCs). (I) Heatmap analysis of log 2 expression fold changes (FC) of immunomodulatory genes in TK173 cells and ccRCC OTSCs (N/A – not announced). (J&K) IF validation of COL6 regulation in cabozantinib-treated ccRCC OTSCs. Images show IF staining for Nuclei by Hoechst (blue), CK (yellow) and COL6A1 (violet) of OTSCs treated with the indicated drugs. Quantification of COL6A1-positive areas in OTSCs of 10 ccRCC patients (dots indicate individual patients analyzed, ratio paired t test). (L) Schematic summary illustrating the findings of the study, highlighting COL6 expression in tumor stroma as well as the remodeling of the ECM architecture in dependence of COL6 abundance and the subsequent implications for cancer and immune cells (Created in BioRender. Schell, C. (2026) https://BioRender.com/x5sqb3y ).

Article Snippet: Inhibitors used and respective working concentrations are 5 μM cabozantinib (S1119, Selleck Chemicals, Houston, TX, USA), 10 μM sunitinib (S1042, Selleck Chemicals, Houston, TX, USA) and 10 μM temsirolimus (S1044, Selleck Chemicals, Houston, TX, USA), medium was changed every second day.

Techniques: Expressing, Fluorescence, Comparison, Staining, Synthesized, RNA Sequencing, Control, Gene Expression, Biomarker Discovery

Journal: Indonesian Journal of Pharmaceutics

Article Title: Impact of Sample Preparation Methods on LC-MS/MS Analysis of Molecular Targeted Drugs

doi: 10.24198/idjp.v7i1.60748

Figure Lengend Snippet: Figure 1. Typical chromatograms of molecular targeted drugs in human serum. (a) M18, (b) N-desethyl sunitinib, (c) gilteritinib, (d) abemaciclib, (e) pazopanib, (f) tirabrutinib, (g) ponatinib, (h) cabozantinib, (i) M20, (j) M2, (k) sunitinib, (l) dasatinib, (m) axitinib, (n) osimertinib, (o) asciminib

Article Snippet: Abemaciclib and cabozantinib were purchased from LKT Laboratories, Inc. (St. Paul, Minnesota, USA).

Techniques:

Journal: Oncotarget

Article Title: Targeting the receptor tyrosine kinase RET in combination with aromatase inhibitors in ER positive breast cancer xenografts

doi: 10.18632/oncotarget.11826

Figure Lengend Snippet: Wild-type MCF7 cells were grown in complete medium (E2+) or in E2-deprived DCC medium (E2-) for 3 days, serum-starved for the last 24 hours and pre-treated with the indicated concentrations of A. sunitinib, B. cabozantinib, or C. NVP-BBT594 for 90 minutes before 30 minutes GDNF (20 ng/ml) stimulation. Total cell lysates were subjected to western blotting using the indicated antibodies. Tubulin was used as a loading control. Molecular size markers are in kDa.

Article Snippet: Cabozantinib and sunitinib were purchased from Tocris Bioscience.

Techniques: Western Blot, Control

Journal: Hepatology International

Article Title: Fibroblast growth factor inhibition by molecular-targeted agents mitigates immunosuppressive tissue microenvironment in hepatocellular carcinoma

doi: 10.1007/s12072-023-10603-z

Figure Lengend Snippet: The tumor immune microenvironment was altered by treatment with anti-VEGFR-2 antibody, regorafenib, or cabozantinib. Representative micrographs (left panel) and quantification (right panel) of CD3-positive, CD8-positive, Granzyme B-positive, and Foxp3-positive cells; F4/80-positive, Arginase-1-positive,and CD11c-positive areas; and NK1.1-positive cells in the VT, VEGFR2 antibody, regorafenib, and cabozantinib groups. Arrowheads represent positive cells. * p < 0.05, ** p < 0.01 vs. VT, one-way ANOVA. Data are presented as mean ± SEM. VT vehicle treatment, VEGFR2 vascular endothelial growth factor receptor 2, ns no significance

Article Snippet: The treatment groups were as follows: (I) Sorafenib; sorafenib tosylate (CAS No.: 475207-59-1; purchased from Santa Cruz Biotechnology, Inc., TX, USA), administered 30 mg/kg orally/once daily; (II) Lenvatinib; lenvatinib mesylate (CAS No.: 417716-92-8; kindly provided by Eisai co. ltd., Tokyo, Japan), administered 10 mg/kg/mouse orally/once daily; (III) VEGFR2 (VEGF receptor 2) antibody; DC101, an anti-VEGFR2 antibody, purchased from Bio X Cell (Lebanon, NH, USA), administered intraperitoneally thrice/week at a dose of 40 mg/kg; (IV) Regorafenib; regorafenib (CAS No.: 755037-03-7; purchased from Tokyo Chemical Industry, Tokyo, Japan), administered 3 mg/kg orally/once daily; (V) Cabozantinib; cabozantinib malate (CAS No.: 849217-68-1; purchased from ChemScene, Monmouth Junction, NJ, USA), administered 30 mg/kg orally/once daily; (VI) FGFR (FGF receptor) inhibitor; AZD4547, FGFR-1/2/3/4 inhibitor (CAS No.: 1035270-39-3; purchased from ChemScene), administered 12.5 mg/kg intraperitoneally/once daily; (VII) VT (vehicle treatment); PBS as vehicle was administered orally or intraperitoneally.

Techniques:

Journal: Hepatology International

Article Title: Fibroblast growth factor inhibition by molecular-targeted agents mitigates immunosuppressive tissue microenvironment in hepatocellular carcinoma

doi: 10.1007/s12072-023-10603-z

Figure Lengend Snippet: Immune checkpoint molecules altered by MTA treatment. Representative micrographs (upper panel) and quantification (lower panel) of PD-1- and PD-L1-positive cells in VT, sorafenib, lenvatinib, VEGFR2 antibody, and regorafenib cabozantinib groups. Arrowheads represent positive cells. * p < 0.05, ** p < 0.01 vs. VT, one-way ANOVA. Data are presented as mean ± SEM. VT vehicle treatment, VEGFR2 vascular endothelial growth factor receptor 2, ns not significant, PD-1 programmed cell death-1, PD-L1 programmed cell death ligand 1

Article Snippet: The treatment groups were as follows: (I) Sorafenib; sorafenib tosylate (CAS No.: 475207-59-1; purchased from Santa Cruz Biotechnology, Inc., TX, USA), administered 30 mg/kg orally/once daily; (II) Lenvatinib; lenvatinib mesylate (CAS No.: 417716-92-8; kindly provided by Eisai co. ltd., Tokyo, Japan), administered 10 mg/kg/mouse orally/once daily; (III) VEGFR2 (VEGF receptor 2) antibody; DC101, an anti-VEGFR2 antibody, purchased from Bio X Cell (Lebanon, NH, USA), administered intraperitoneally thrice/week at a dose of 40 mg/kg; (IV) Regorafenib; regorafenib (CAS No.: 755037-03-7; purchased from Tokyo Chemical Industry, Tokyo, Japan), administered 3 mg/kg orally/once daily; (V) Cabozantinib; cabozantinib malate (CAS No.: 849217-68-1; purchased from ChemScene, Monmouth Junction, NJ, USA), administered 30 mg/kg orally/once daily; (VI) FGFR (FGF receptor) inhibitor; AZD4547, FGFR-1/2/3/4 inhibitor (CAS No.: 1035270-39-3; purchased from ChemScene), administered 12.5 mg/kg intraperitoneally/once daily; (VII) VT (vehicle treatment); PBS as vehicle was administered orally or intraperitoneally.

Techniques:

Journal: Cancers

Article Title: Immune Checkpoint Inhibition in Advanced Non-Clear Cell Renal Cell Carcinoma: Leveraging Success from Clear Cell Histology into New Opportunities

doi: 10.3390/cancers13153652

Figure Lengend Snippet: Completed prospective single-arm studies of immunotherapy in nccRCC.

Article Snippet: We have particular enthusiasm for the use of cabozantinib in combination with ICI, as it is a multitarget TKI that impacts tumor-associated macrophages, increases affected T-cells, blocks the mobilization of immunosuppressive cells, and creates an immune-permissive tumor microenvironment, with the hopes of ‘awakening’ immunologically cold tumors.

Techniques: Translocation Assay

Journal: Cancers

Article Title: Immune Checkpoint Inhibition in Advanced Non-Clear Cell Renal Cell Carcinoma: Leveraging Success from Clear Cell Histology into New Opportunities

doi: 10.3390/cancers13153652

Figure Lengend Snippet: Active prospective studies for patients with nccRCC employing immunotherapy.

Article Snippet: We have particular enthusiasm for the use of cabozantinib in combination with ICI, as it is a multitarget TKI that impacts tumor-associated macrophages, increases affected T-cells, blocks the mobilization of immunosuppressive cells, and creates an immune-permissive tumor microenvironment, with the hopes of ‘awakening’ immunologically cold tumors.

Techniques: Translocation Assay, Biomarker Discovery

Journal: NPJ Systems Biology and Applications

Article Title: Mechanistically detailed systems biology modeling of the HGF/Met pathway in hepatocellular carcinoma

doi: 10.1038/s41540-019-0107-2

Figure Lengend Snippet: Diagram of the main molecular interactions implemented in the model. The diagram illustrates surface molecules and their interactions (on the left), as well as the intracellular downstream signaling to ERK (extracellular-regulated kinase) and Akt (on the right). Surface Met can bind hepatocyte growth factor (HGF) and get activated in the absence of α5β1 integrin that leads to rapid internalization and degradation, whereas integrin-bound Met has lower internalization/degradation and higher recycling rates. In addition to integrin-binding peptide (AXT050) that dissociates the Met/α5β1 complex, effect of anti-Met (cabozantinib), anti-HGF (rilotumumab), and Raf inhibitor (sorafenib) drugs were explored in this study

Article Snippet: The next day, cultures were treated with 25 μM AXT050 or DMSO vehicle for 90 min, followed by treatment with either 200 nM sorafenib tosylate (ChemScene, Monmouth Junction, NJ) or 100 nM cabozantinib malate (APExBIO, Houston, TX) or DMSO vehicle.

Techniques: Binding Assay

Journal: NPJ Systems Biology and Applications

Article Title: Mechanistically detailed systems biology modeling of the HGF/Met pathway in hepatocellular carcinoma

doi: 10.1038/s41540-019-0107-2

Figure Lengend Snippet: Experimental data and comparison with model. Phosphorylation of Akt ( a ) and ERK (extracellular-regulated kinase) ( b ) and were measured for hepatocyte growth factor (HGF) treatment along with AXT050, sorafenib and cabozantinib or AXT050 + sorafenib and AXT05 + cabozantinib. Cropped images of the western blots and the experimental data (blue) were normalized to HGF control for each gel and is shown as mean ± SEM ( n = 4, except for AXT050 + sorafenib with n = 3). Uncropped images of the sample blots are available in the supplements (Supplementary Fig. ). The modeling results are shown as median (bar graph) and the data points for all the Monte Carlo resampled cases. Experimental data were compared using analysis of variance with Tukey’s multiple comparisons correction, while non-parametric Kruskal–Wallis test with Bonferroni correction was used to compare modeled groups. Significance was assumed at corrected p < 0.05. Bottom row compares the significant changes between model and experiments

Article Snippet: The next day, cultures were treated with 25 μM AXT050 or DMSO vehicle for 90 min, followed by treatment with either 200 nM sorafenib tosylate (ChemScene, Monmouth Junction, NJ) or 100 nM cabozantinib malate (APExBIO, Houston, TX) or DMSO vehicle.

Techniques: Comparison, Phospho-proteomics, Western Blot, Control

Journal: NPJ Systems Biology and Applications

Article Title: Mechanistically detailed systems biology modeling of the HGF/Met pathway in hepatocellular carcinoma

doi: 10.1038/s41540-019-0107-2

Figure Lengend Snippet: Combination of AXT050 peptide with other drugs targeting the hepatocyte growth factor (HGF) pathway. Combination of AXT050 peptide with sorafenib ( a ), cabozantinib ( b ), and rilotumumab ( c ) along with their respective isobolograms are illustrated here. In the first column, arrows show the direction of increase in the inhibitor concentration, which was varied in the range of 1–1000 nM for sorafenib, 1–1000 nM for cabozantinib, and 0.01–10 nM for rilotumumab. Phosphorylation of Akt (blue) and ERK (extracellular-regulated kinase) (green) are shown for simulations of different levels of each inhibitor (first column). Dose-dependent changes in Akt and ERK phosphorylation at early timepoint of 15 min (second column) and late timepoint of 120 min (third column) illustrates the inhibition potential of each simulation drug as monotherapy. The combination of AXT050 peptide with each of the drugs was simulated over the therapeutic range, half-maximal inhibitory concentrations (IC 50 s) were calculated, and isobolograms were produced for 15 min (fourth column) and 120 min (fifth column) for phosphorylated Akt and ERK, to be able to visually explore synergistic combinations. All simulations are under 40 ng/ml HGF treatment

Article Snippet: The next day, cultures were treated with 25 μM AXT050 or DMSO vehicle for 90 min, followed by treatment with either 200 nM sorafenib tosylate (ChemScene, Monmouth Junction, NJ) or 100 nM cabozantinib malate (APExBIO, Houston, TX) or DMSO vehicle.

Techniques: Concentration Assay, Phospho-proteomics, Inhibition, Produced

Journal: NPJ Systems Biology and Applications

Article Title: Mechanistically detailed systems biology modeling of the HGF/Met pathway in hepatocellular carcinoma

doi: 10.1038/s41540-019-0107-2

Figure Lengend Snippet: Patient-specific response to combination treatment. Assuming phosphorylation of Akt or ERK (extracellular-regulated kinase) as outputs, the synergistic potency (log( α 2 ) > 0) and synergistic efficacy ( β obs > 0) were calculated to measure the synergy between the peptide (AXT050) and three drugs against the HGF pathway (sorafenib, cabozantinib, and rilotumumab). Log( α 2 ) > 0 shows synergistic potency and β obs > 0 shows synergistic efficacy. Each column shows the data for a patient from TCGA ordered the same as patients in Fig.

Article Snippet: The next day, cultures were treated with 25 μM AXT050 or DMSO vehicle for 90 min, followed by treatment with either 200 nM sorafenib tosylate (ChemScene, Monmouth Junction, NJ) or 100 nM cabozantinib malate (APExBIO, Houston, TX) or DMSO vehicle.

Techniques: Phospho-proteomics