Journal: Cancer Cell International

Article Title: PHI-501, a dual inhibitor of RAF and DDR1/2, overcomes MAPK drug resistance in Melanoma

doi: 10.1186/s12935-026-04271-w

Figure Lengend Snippet: MAPK inhibitor-resistant melanoma cells exhibit enhanced DDR1/2 signaling. ( A ) Clonogenic assay showing the validation of drug-resistant cell lines. ( B ) Quantification of clonogenic assay shown in Fig. 1A. Data are presented as relative colony formation (%) normalized to the control group and expressed as the mean ± SEM, n = 3 replicates. Statistical significance was determined by two-way ANOVA. * p < 0.05, # p < 0.001, † p < 0.001, ‡ p < 0.0001. ( C ) Cell viability assay of RAF and MEK inhibitors in parental cells and drug-resistant cells for 48 h. Data are presented as the mean ± SEM, n = 3 replicates. ( D ) Western blot analysis of pERK and pAKT signaling responses in parental and resistant melanoma cells following 48-h treatment with vehicle or the corresponding resistance-selecting drug(s) at 1 µM. ( E ) Bubble plot representing Gene Set Enrichment Analysis (GSEA) using hallmark gene set comparing parental and resistant melanoma cells. Pathway enrichment was calculated using GSEA, with color indicating NES (blue = downregulated, red = upregulated) and bubble size representing −log10(p-value). ( F ) SK-MEL-2 and SK-MEL-2BR cells were stimulated with type I collagen (40 µg/ml) for 18 h to activate DDR signaling

Article Snippet: The membranes were incubated overnight at 4 °C with primary antibodies diluted in 5% BSA in TBST as indicated in the text: p-DDR1 (Cell Signaling Technology, CST14531 ), p-DDR1/2 (R&D Systems, MAB25382), p-AKT (Cell Signaling Technology, CST4058), AKT (Cell Signaling Technology, CST9272), p-MEK (Cell Signaling Technology, CST9121), p-ERK (Cell Signaling Technology, CST9101), ERK (Cell Signaling Technology, CST9102), Cyclin D1(Cell Signaling Technology, CST2978), and Survivin (Cell Signaling Technology, CST2808).

Techniques: Clonogenic Assay, Biomarker Discovery, Control, Viability Assay, Western Blot

Journal: Cancer Cell International

Article Title: PHI-501, a dual inhibitor of RAF and DDR1/2, overcomes MAPK drug resistance in Melanoma

doi: 10.1186/s12935-026-04271-w

Figure Lengend Snippet: DDR1 and DDR2 are associated with MAPK pathway activation and therapeutic resistance in melanoma. ( A ) Kaplan–Meier survival analysis showing patient outcomes based on DDR1 and DDR2 expression levels across all TCGA cancer types. Patients were stratified into high (top 25%) and low (bottom 25%) expression groups, and overall survival (OS) was analyzed. ( B ) Proteomic analysis of BRAF/NRAS-mutant SKCM. Box plots demonstrate differential expression of AKT and phosphorylated MEK1 (pMEK1-S217/S221) between wild-type and mutant groups. ( C ) Correlation heatmaps between DDR1/2 and key genes in the MAPK and AKT signaling pathways in TCGA-SKCM samples. Color intensity represents the correlation value, with red indicating a positive correlation. Significance levels are indicated by asterisks (* p < 0.05, ** p < 0.01, *** p < 0.001). ( D ) Correlation analysis revealing DDR1 expression (DepMap) and MAPK pathway inhibitor sensitivity (GDSC2) in melanoma cell lines. Scatter plots depicting correlations between DDR1 expression levels and IC50 to Dabrafenib (left) and Trametinib (right)

Article Snippet: The membranes were incubated overnight at 4 °C with primary antibodies diluted in 5% BSA in TBST as indicated in the text: p-DDR1 (Cell Signaling Technology, CST14531 ), p-DDR1/2 (R&D Systems, MAB25382), p-AKT (Cell Signaling Technology, CST4058), AKT (Cell Signaling Technology, CST9272), p-MEK (Cell Signaling Technology, CST9121), p-ERK (Cell Signaling Technology, CST9101), ERK (Cell Signaling Technology, CST9102), Cyclin D1(Cell Signaling Technology, CST2978), and Survivin (Cell Signaling Technology, CST2808).

Techniques: Activation Assay, Expressing, Mutagenesis, Quantitative Proteomics, Protein-Protein interactions

Journal: medRxiv

Article Title: A brain-persistent DDR2-degrading antibody reverses Alzheimer’s pathologies by restoring brain fluid dynamics and metabolic clearance

doi: 10.64898/2026.03.17.26348575

Figure Lengend Snippet: (A) CBF assessed by LSCI in WT, APP/PS1, and astrocyte specific Ddr2 overexpressing APP/PS1 mice. Left: Representative pseudocolor perfusion maps. Right: Quantification of relative perfusion units (Mean ± SEM; ** p < 0.01, one-way ANOVA). (B) Correlation between CBF (from A) and cortical Ddr2 mRNA levels (qPCR) across individual mice (Pearson r = −0.6081, p < 0.01). (C) In vivo (top) and ex vivo (bottom) whole brain fluorescence imaging after intravenous injection of the DDR2 targeting probe 1A12-mCherry. (D) Validation of 1A12-mCherry brain delivery and target specificity: Ex vivo brain sections for intrinsic mCherry fluorescence (red), anti-His tag immunofluorescence staining (green), and anti-DDR2 antibody HL2 staining (purple), the areas outlined by white squares are magnified in the adjacent panels. Scale bar: 30 μm for original images and 10 μm for enlarged images. (E) Schematic of the sequential probe injection protocol for vascular perfusion assessment: 1A12-mCherry followed 40 min later by Dextran-FITC (70 kDa). (F) Whole brain fluorescence imaging of vascular perfusion with Dextran-FITC (70 kDa). (G) Two photon microscopy of cortical vasculature. Representative images show mCherry signal (red) and dextran-FITC vasculature (green) in WT, APP/PS1, and APP/PS1-DDR2 mice, scale bars: 50 μm. (H) Representative two-photon microscopy images of vascular leakage after injection of dextran-FITC (4 kDa, green) and dextran-RB (70 kDa, red), scale bars: 50 μm. (I) Ventricular morphology analyzed by MRI based volumetric reconstruction. Left: Representative images of lateral ventricles from each group. Right: Quantification of lateral ventricular volume (Mean ± SEM; * p < 0.05, ** p < 0.01, one-way ANOVA). (J) CSF flow assessed by cisterna magna injection of high molecular weight dextran (70 kDa, green). Fluorescence stereo microscope images displaying the spatial distribution of the glymphatic system (green) in the brains ( top row ), and corresponding whole brain fluorescence imaging system scans of the same brains( bottom row ), scale bars: 2 mm.

Article Snippet: The primary antibodies used in this study were as follows: anti-DDR2 (1:1000; Servicebio, GB112568), anti-DDR2 (1:1000, R&D, AF2538), anti-BACE1 (1:50; Cell Signaling Technology, no. 5606), anti-Collagen IV (1:1000; abcam, ab6586), anti-PDGFRβ (1:1000; Cell Signaling Technology, no. 3169), anti-Occludin (1:1000; Cell Signaling Technology, no. 91131), anti-ZO1 (1:1000; abcam, ab276131), anti-β-actin (1:1000; Yeasen, 30102ES60).

Techniques: In Vivo, Ex Vivo, Fluorescence, Imaging, Injection, Biomarker Discovery, Immunofluorescence, Staining, Microscopy, High Molecular Weight