Fig. 8: PPAR-dependent FA metabolism dysregulation correlates with cetuximab resistance in patient-derived HNSCC models. | Nature Communications

Fig. 8: PPAR-dependent FA metabolism dysregulation correlates with cetuximab resistance in patient-derived HNSCC models.

From: PPARα-mediated lipid metabolism reprogramming supports anti-EGFR therapy resistance in head and neck squamous cell carcinoma

Fig. 8

a Schematic representation for the establishment of cetuximab-sensitive and -resistant patient-derived xenograft (PDX) models from treatment-naive HNSCC clinical specimens. Created in BioRender. https://BioRender.com/b56r875. Tumor growth of cetuximab-sensitive (b) and -resistant (c) UCLHN4 PDX in nude mice weekly treated with 30 mg/kg cetuximab or vehicle. Xenografts were considered resistant when tumors reached 200% ±10% of their initial size. d, e Individual GSEA plots of FA metabolism-related pathways in RNA-seq data from cetuximab-sensitive and -resistant UCLHN4 PDX (N = 3 for each condition). f mRNA expression for CD36 in cetuximab-sensitive and -resistant UCLHN4 PDX (N = 3). Representative tumor slides (g) and quantification (h) for anti-CD36 immunohistochemistry on tissue sections from cetuximab-sensitive and -resistant UCLHN4 PDX. Scale bar: 100 µm (N = 4). Follow-up of tumor growth (i) and relative tumor size at day 15 (j) for cetuximab-resistant UCLHN4 PDX in nude mice treated with 30 mg/kg cetuximab in combination with either 40 mg/kg etomoxir or 20 mg/kg GW6471. k Schematic representation for the clinical workflow of the window-of-opportunity study with HNSCC patients treated for 14 days with cetuximab. 18FDG-PET scan was carried out before and after treatment and enabled to discriminate between partial metabolic response (PMR) and stable metabolic disease (SMD). Created in BioRender. https://BioRender.com/o74h220. l GSEA plot of the PPARα-related gene signature in RNA-seq data from cetuximab-treated HNSCC patients (SMD vs PMR) (N = 15). Data are plotted as the means ± SEM. N indicates the number of independent biological experiments and n indicates the number of technical replicates (when >1). Significance was determined by two-tailed unpaired Student’s t-test (h), one-way ANOVA with Dunnett’s multiple comparison test (j) or two-way ANOVA with Sidák’s multiple comparison test (f). P-values as indicated or ***P < 0.001. Source data are provided as a Source Data file.

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