Journal: Signal Transduction and Targeted Therapy

Article Title: Dual-targeting pharmacological UFMylation inhibition reprograms tumor and immune microenvironments to achieve long-term glioblastoma regression

doi: 10.1038/s41392-026-02819-w

Figure Lengend Snippet: Identification of Osimertinib and CP-24 as potent disruptors of the DDRGK1-UFL1 interaction. a Schematic representation of the experimental design. b Cherry-picked compounds from virtual screening. Molecules with docking scores < −7.5 and molecular weights < 600 Da were collected as the cherry-picked library for further NanoBRET screening. c High-throughput NanoBRET screening to identify compounds that inhibit the DDRGK1-UFL1 interaction. d Chemical structure of Osimertinib. e Chemical structure of CP-24. f Osimertinib inhibited the NanoBRET signal from the DDRGK1-UFL1 interaction in a dose-dependent manner ( N = 6). Data are presented as mean ± s.d. g CP-24 inhibited the NanoBRET signal from the DDRGK1-UFL1 interaction in a dose-dependent manner ( N = 3). Data are presented as mean ± s.d

Article Snippet: GBM cells were treated with DMSO, 1 μM, 5 μM, 10 μM Osimertinib, 5 μM Afatinib (MedChemExpress, HY-10261B), 5 μM Erlotinib (MedChemExpress, HY-50896), 5 μM Gefitinib (MedChemExpress, HY-50895), 5 μM Tinodasertib (MedChemExpress, HY-112424), 5 μM Tomiversotib (MedChemExpress, HY-100022), 5 μM WZ4002 (MedChemExpress, HY-12026), or 10 μM, 20 μM, 40 μM CP-24 for 24 h prior to sample collection.

Techniques: High Throughput Screening Assay

Journal: Signal Transduction and Targeted Therapy

Article Title: Dual-targeting pharmacological UFMylation inhibition reprograms tumor and immune microenvironments to achieve long-term glioblastoma regression

doi: 10.1038/s41392-026-02819-w

Figure Lengend Snippet: Binding of Osimertinib and CP-24 to DDRGK1. ITC analysis showing heat release upon Osimertinib ( a , b ) or CP-24 ( c , d ) binding to purified DDRGK1 Δ216–314 . ITC analysis showing heat release from purified UFL1 Δ1–212 binding to purified DDRGK1 Δ216–314 , which was pre-incubated with DMSO ( e , f ), Osimertinib ( g , h ), or CP-24 ( i , j ). co-IP showing interaction of DDRGK1 with UFL1 when cells were treated with DMSO, Osimertinib, or CP-24 ( k ), with quantification shown in ( l – n ). Statistical significance was determined using t -tests; N = 3. For m , Osimertinib vs . DMSO: p = 0.0313, CP-24 vs . DMSO: p = 0.0272. For n , Osimertinib vs . DMSO: p = 0.0206, CP-24 vs . DMSO: p = 0.0348. Other comparisons: ns. Data are presented as mean ± s.d. Molecular weight changes of DDRGK1 Δ216–314 after incubation with Osimertinib ( o ) or CP-24 ( p ) compared to DMSO. q Workflow for MS analysis to identify Osimertinib binding sites on DDRGK1 Δ216–314 . r MS analysis identified peptides generated by trypsin digestion of DDRGK1 Δ216–314 . Lysine (K) and Arginine (R) served as trypsin digestion sites. s – t Osimertinib binding sites on DDRGK1 Δ216–314 identified by MS. u Molecular docking model of Osimertinib binding to Ser226 of DDRGK1 Δ216–314 . v Molecular docking model of Osimertinib binding to Lys227 of DDRGK1 Δ216–314 . w Molecular docking model of CP-24 binding to DDRGK1 Δ216–314

Article Snippet: GBM cells were treated with DMSO, 1 μM, 5 μM, 10 μM Osimertinib, 5 μM Afatinib (MedChemExpress, HY-10261B), 5 μM Erlotinib (MedChemExpress, HY-50896), 5 μM Gefitinib (MedChemExpress, HY-50895), 5 μM Tinodasertib (MedChemExpress, HY-112424), 5 μM Tomiversotib (MedChemExpress, HY-100022), 5 μM WZ4002 (MedChemExpress, HY-12026), or 10 μM, 20 μM, 40 μM CP-24 for 24 h prior to sample collection.

Techniques: Binding Assay, Purification, Incubation, Co-Immunoprecipitation Assay, Molecular Weight, Generated

Journal: Signal Transduction and Targeted Therapy

Article Title: Dual-targeting pharmacological UFMylation inhibition reprograms tumor and immune microenvironments to achieve long-term glioblastoma regression

doi: 10.1038/s41392-026-02819-w

Figure Lengend Snippet: Osimertinib and CP-24 inhibit ER-phagy and induce ER stress as potent UFMylation inhibitors. a – e Osimertinib and CP-24 dose-dependently decreased global UFMylation levels and DDRGK1 protein levels in A172, LN229, U251, and U87 cells. Data in ( b – e ) are presented as mean + s.d. f Schematic illustration showing the ER-phagy detection system. g Osimertinib and CP-24 significantly inhibited starvation-induced ER-phagy, as visualized by confocal imaging. Scale bar: 20 μm. h Quantification of ER-phagy puncta per cell using ImageJ software. Seven images from the control (DMEM + DMSO) group and eight images from each other group were randomly selected for quantification. Statistical significance was determined by one-sided t -test. EBSS + DMSO vs . DMEM + DMSO: p < 0.0001; EBSS + Osimertinib vs . EBSS + DMSO: p < 0.0001; EBSS + CP-24 vs . EBSS + DMSO: p = 0.004. Data are presented as mean ± s.d. i Osimertinib and CP-24 significantly inhibited starvation-induced ER-phagy as revealed by FACS analysis and analyzed by one-sided t -test ( N = 5). EBSS + DMSO vs . DMEM + DMSO: p < 0.0001; EBSS + Osimertinib vs . EBSS + DMSO: p = 0.0006; EBSS + CP-24 vs . EBSS + DMSO: p < 0.0001. Data are presented as mean ± s.d. j Osimertinib and CP-24 reduced the size of DDRGK1-UFL1 aggregation puncta and induced the formation of ER whorl-like structures. Arrows indicate ER whorl-like structures. Scale bar: 20 μm. k Average DDRGK1-UFL1 aggregation puncta size quantified using ImageJ. 6 images per group were analyzed by two-sided t tests. DMSO vs . Osimertinib: p < 0.0001, DMSO vs . CP-24: p = 0.0152. Data are presented as mean ± s.d. l Heatmap showing the upregulation of ER stress-related genes after Osimertinib and CP-24 treatment, as measured by bulk RNA-seq. The heatmap is colored according to z-score-normalized gene transcription levels. m qRT-PCR analysis of the transcription of ER stress-related genes after Osimertinib and CP-24 treatment in A172 cells. Data were analyzed by one-sided t -test ( N = 3). For HSPA5: A172 + Osimertinib vs . A172 + DMSO: p = 0.0003, A172 + CP-24 vs . A172 + DMSO: p < 0.0001; for sXBP1: A172 + Osimertinib vs . A172 + DMSO: p = 0.0098, A172 + CP-24 vs . A172 + DMSO: p < 0.0075; for CANX: A172 + Osimertinib vs . A172 + DMSO: p = 0.0003, A172 + CP-24 vs . A172 + DMSO: p < 0.0001; for ERN1: A172 + Osimertinib vs . A172 + DMSO: p = 0.019; for PERK: A172 + Osimertinib vs . A172 + DMSO: p = 0.0002, A172 + CP-24 vs . A172 + DMSO: p < 0.0001. Other comparisons: not significant (ns). Data are presented as mean ± s.d. n qRT-PCR analysis of the transcription of ER stress-related genes after Osimertinib and CP-24 treatment in U87 cells. Data were analyzed by one-sided t -test ( N = 3). For sXBP1: U87 + CP-24 vs . U87 + DMSO: p < 0.0001; for CANX: U87 + Osimertinib vs . U87 + DMSO: p = 0.0006, U87 + CP-24 vs . U87 + DMSO: p = 0.0003; for PERK: U87 + Osimertinib vs . U87 + DMSO: p = 0.0002, U87 + CP-24 vs . U87 + DMSO: p < 0.0001. Other comparisons: ns. Data are presented as mean ± s.d

Article Snippet: GBM cells were treated with DMSO, 1 μM, 5 μM, 10 μM Osimertinib, 5 μM Afatinib (MedChemExpress, HY-10261B), 5 μM Erlotinib (MedChemExpress, HY-50896), 5 μM Gefitinib (MedChemExpress, HY-50895), 5 μM Tinodasertib (MedChemExpress, HY-112424), 5 μM Tomiversotib (MedChemExpress, HY-100022), 5 μM WZ4002 (MedChemExpress, HY-12026), or 10 μM, 20 μM, 40 μM CP-24 for 24 h prior to sample collection.

Techniques: Imaging, Software, Control, RNA Sequencing, Quantitative RT-PCR

Journal: Signal Transduction and Targeted Therapy

Article Title: Dual-targeting pharmacological UFMylation inhibition reprograms tumor and immune microenvironments to achieve long-term glioblastoma regression

doi: 10.1038/s41392-026-02819-w

Figure Lengend Snippet: Osimertinib and CP-24 exhibit pleiotropic anti-tumor effects in vitro. a DDRGK1 expression level negatively correlates with patient survival, as analyzed by log-rank test (data from the CGGA database). b DDRGK1 expression level negatively correlates with patient survival, as analyzed by log-rank test (data from the GEPIA database). c DDRGK1 expression level negatively correlates with patient survival, as analyzed by log-rank test (data from the TCGA database). d DDRGK1 expression level negatively correlates with patient survival in IDH wild type patients, as analyzed by log-rank test (data from the CGGA database). e Relationship between DDRGK1 expression level and patient survival in IDH mutant patients, as analyzed by log-rank test (data from the CGGA database). f DDRGK1 expression level positively correlates with glioma WHO malignancy grade, as analyzed by ANOVA test (data from the CGGA database). g DDRGK1 expression level positively correlates with patient age, as analyzed by two-sided t -test (data from the CGGA database). Osimertinib ( h ) and CP-24 ( i ) induced cell death in A172, LN229, U251, and U87 GBM cells ( N = 3). Data are presented as mean ± s.d. Osimertinib ( j ) and CP-24 ( k ) induced cell death in GBM 322, GBM324, GBM326, and GBM375 GBM patient-derived cells ( N = 3). Data are presented as mean ± s.d. l Heatmap showing the upregulation of apoptosis-related genes after Osimertinib and CP-24 treatment. The heatmap is colored according to z-score-normalized gene transcription levels. m Heatmap showing the downregulation of cell proliferation-related genes after Osimertinib and CP-24 treatment. The heatmap is colored according to z-score-normalized gene transcription levels. n TMZ-resistant A172 cells (TMZ + A172) were more sensitive to Osimertinib than parental A172 cells, as analyzed by one-sided t -test ( N = 6). A172 + TMZ vs . A172: p = 0.0472; U87 + TMZ vs . U87: p = 0.1244. Data are presented as mean ± s.d. o TMZ-resistant A172 (A172 + TMZ) and U87 (U87 + TMZ) cells were more sensitive to CP-24 than parental A172 and U87 cells, as analyzed by one-sided t -test ( N = 6). A172 + TMZ vs . A172: p = 0.0073; U87 + TMZ vs . U87: p = 0.0096. Data are presented as mean ± s.d. p Irradiated A172 (A172 + IR) and U87 (U87 + IR) cells were more sensitive to Osimertinib than parental A172 and U87 cells, as analyzed by one-sided t -test ( N = 3). A172 + IR vs . A172: p = 0.0267; U87 + IR vs . U87: p = 0.0361. Data are presented as mean ± s.d. q Irradiated A172 and U87 cells were more sensitive to CP-24 than parental A172 and U87 cells, as analyzed by one-sided t -test ( N = 3). A172 + IR vs . A172: p = 0.0010; U87 + IR vs . U87: p = 0.0006. Data are presented as mean ± s.d. r Heatmap showing the downregulation of DNA repair-related genes following Osimertinib and CP-24 treatment. The heatmap is colored according to z-score-normalized gene transcription levels. s qRT-PCR results showing the effects of Osimertinib and CP-24 in THP-1-derived macrophages, as analyzed by t -tests ( N = 3). Osimertinib vs . DMSO: CD68: p = 0.0001, CD86: p = 0.0072, CD80: p = 0.0330, ITGAX: p = 0.0099, CXCL16: p = 0.0004. CP-24 vs . DMSO: CD68: p = 0.0003, CD86: p = 0.0001, CD80: p = 0.0002, ITGAX: p = 0.0006, CXCL16: p = 0.0002. Other comparisons: ns. Data are presented as mean ± s.d. t qRT-PCR results showing the effects of Osimertinib and CP-24 on human primary bone marrow-derived macrophages, as analyzed by t -tests ( N = 3). Osimertinib vs . DMSO: CD68: p = 0.0008, CD80: p = 0.0335, ITGAX: p < 0.0001, CXCL16: p = 0.0043. CP-24 vs . DMSO: CD68: p = 0.0003, CD86: p = 0.0009, CD80: p = 0.0236, ITGAX: p = 0.0008, CXCL16: p = 0.0001. Other comparisons: ns. Data are presented as mean ± s.d

Article Snippet: GBM cells were treated with DMSO, 1 μM, 5 μM, 10 μM Osimertinib, 5 μM Afatinib (MedChemExpress, HY-10261B), 5 μM Erlotinib (MedChemExpress, HY-50896), 5 μM Gefitinib (MedChemExpress, HY-50895), 5 μM Tinodasertib (MedChemExpress, HY-112424), 5 μM Tomiversotib (MedChemExpress, HY-100022), 5 μM WZ4002 (MedChemExpress, HY-12026), or 10 μM, 20 μM, 40 μM CP-24 for 24 h prior to sample collection.

Techniques: In Vitro, Expressing, Mutagenesis, Derivative Assay, Irradiation, Quantitative RT-PCR

Journal: Signal Transduction and Targeted Therapy

Article Title: Dual-targeting pharmacological UFMylation inhibition reprograms tumor and immune microenvironments to achieve long-term glioblastoma regression

doi: 10.1038/s41392-026-02819-w

Figure Lengend Snippet: Osimertinib exhibits pleiotropic anti-tumor effects in vivo. a Schematic illustration of the experimental protocol used to evaluate the anti-tumor effects of Osimertinib in NCG orthotopic U87 xenograft GBM model. b Tumor burden in vehicle- (CTR) or Osimertinib-treated NCG mice bearing orthotopic GBM xenograft was monitored by whole-body bioluminescence imaging (BLI). Data were analyzed by two-sided t -test ( N = 12), p = 0.0372. Data are presented as mean + s.d. c Survival of vehicle- or Osimertinib-treated NCG mice bearing orthotopic GBM xenograft was monitored. Data were analyzed by log-rank test ( N = 12), p = 0.0395. d Schematic illustration of the experimental protocol used to evaluate the anti-tumor effects of Osimertinib in an orthotopic GBM375 patient-derived xenograft (PDX) GBM model established in BALB/c nude mice. e Tumor burden in CTR or Osimertinib-treated BALB/c nude mice bearing orthotopic GBM PDX tumors was monitored by whole-body bioluminescence imaging (BLI). Data were analyzed by two-sided t -test ( N = 10), p = 0.0470. Data are presented as mean + s.d. f Survival of CTR or Osimertinib-treated BALB/c nude mice bearing orthotopic PDX GBM tumors was monitored. Data were analyzed by log-rank test ( N = 10), p = 0.0480. g Schematic illustration of the experimental protocol used to evaluate the anti-tumor effects of Osimertinib a syngeneic orthotopic GL261 GBM model established in C57BL/6J mice. h Tumor burden in CTR or Osimertinib-treated C57BL/6J mice bearing orthotopic GL261 GBM tumors monitored by whole-body bioluminescence imaging (BLI). Data were analyzed by Mann–Whitney test ( N = 14), p = 0.0091. i Survival of CTR or Osimertinib-treated C57BL/6J mice bearing orthotopic GL261 GBM tumors was monitored. Data were analyzed by log-rank test ( N = 14), p = 0.0002. j PD-1 expression pattern in tumor-infiltrating CD3 + CD8 + T cells. k Quantitative analysis of ( j ) showing that Osimertinib treatment decreased the proportion of PD-1 + CD3 + CD8 + T cells among tumor-infiltrating CD3 + CD8 + T cells. Data were analyzed by one-sided t -test ( N = 5), p < 0.0001. l Quantitative analysis of ( j ) showing that Osimertinib treatment decreased PD-1 expression level in tumor-infiltrating CD3 + CD8 + T cells. Data were analyzed by one-sided t -test ( N = 5), p = 0.0076. MFI Mean fluorescence intensity. m PD-1 expression pattern in tumor-infiltrating CD3 + CD4 + T cells. n Quantitative analysis of ( m ) showing that Osimertinib treatment decreased the proportion of PD-1 + CD3 + CD4 + T cells among tumor-infiltrating CD3 + CD4 + T cells. Data were analyzed by one-sided t -test ( N = 5), p = 0.0114. o Quantitative analysis of ( m ) showing the effects of Osimertinib treatment on PD-1 expression level in tumor-infiltrating CD3 + CD4 + T cells. Data were analyzed by one-sided t -test ( N = 5), not significant (ns). MFI: Mean fluorescence intensity. p , q Global UFMylation level in tumor cells ( p ). Data were analyzed by two-sided t test ( q , N = 5). p < 0.0001. Data are presented as mean ± s.d. r , s Global UFMylation level in tumor-infiltrating CD45 + CD3 - immune cells ( r ). Data were analyzed by two-sided t test ( s , N = 5). p = 0.0493. Data are presented as mean ± s.d. t , u Global UFMylation level in tumor-infiltrating CD45 + CD3 + CD4 + T cells ( t ). Data were analyzed by two-sided t test ( u , N = 5). p = 0.0016. Data are presented as mean ± s.d. v , w Global UFMylation level in tumor-infiltrating CD45 + CD3 + CD8 + T cells ( v ). Data were analyzed by two-sided t test ( w , N = 5). p = 0.0002. Data are presented as mean ± s.d

Article Snippet: GBM cells were treated with DMSO, 1 μM, 5 μM, 10 μM Osimertinib, 5 μM Afatinib (MedChemExpress, HY-10261B), 5 μM Erlotinib (MedChemExpress, HY-50896), 5 μM Gefitinib (MedChemExpress, HY-50895), 5 μM Tinodasertib (MedChemExpress, HY-112424), 5 μM Tomiversotib (MedChemExpress, HY-100022), 5 μM WZ4002 (MedChemExpress, HY-12026), or 10 μM, 20 μM, 40 μM CP-24 for 24 h prior to sample collection.

Techniques: In Vivo, Imaging, Derivative Assay, MANN-WHITNEY, Expressing, Fluorescence

Journal: Signal Transduction and Targeted Therapy

Article Title: Dual-targeting pharmacological UFMylation inhibition reprograms tumor and immune microenvironments to achieve long-term glioblastoma regression

doi: 10.1038/s41392-026-02819-w

Figure Lengend Snippet: Long-term immune memory and prevention of glioblastoma recurrence. a Schematic illustration of the experimental protocol used to assess the anti-GBM immune memory in Osimertinib-treated tumor-free C57BL/6J mice. b Tumor burden in control (CTR) or Osimertinib-treated tumor-free mice, monitored by whole-body bioluminescence imaging (BLI). Percentage of naïve, effector, and memory CD3 + CD8 + T cells ( c ) and CD3 + CD4 + T cells ( d ) after 2 days of tumor rechallenge in CTR or Osimertinib-treated tumor-free mice. e Expansion of CD3 + CD8 + effector T cells after tumor rechallenge in CTR or Osimertinib-treated tumor-free mice. Data were analyzed by one-sided t -test ( N = 6), p = 0.0060. Data are presented as mean ± s.d. f Expansion of CD3 + CD8 + memory T cells after tumor rechallenge in CTR or Osimertinib-treated tumor-free mice. Data were analyzed by one-sided t -test ( N = 6), p < 0.0001. Data are presented as mean ± s.d. g Percentage of CD3 + CD8 + naïve T cells decreased after tumor rechallenge in CTR or Osimertinib-treated tumor-free mice. Data were analyzed by one-sided t -test ( N = 6), p < 0.0001. Data are presented as mean ± s.d. h Expansion of CD3 + CD4 + effector T cells after tumor rechallenge in tumor-free mice. Data were analyzed by one-sided t -test ( N = 6), p < 0.0001. Data are presented as mean ± s.d. i No significant change in the percentage of CD3 + CD4 + memory T cells after tumor rechallenge in CTR or Osimertinib-treated tumor-free mice. Data were analyzed by one-sided t -test ( N = 6), ns. Data are presented as mean ± s.d. j Percentage of CD3 + CD4 + naïve T cells decreased after tumor rechallenge in CTR or Osimertinib-treated tumor-free mice. Data were analyzed by one-sided t -test ( N = 6), p = 0.0147. Data are presented as mean ± s.d

Article Snippet: GBM cells were treated with DMSO, 1 μM, 5 μM, 10 μM Osimertinib, 5 μM Afatinib (MedChemExpress, HY-10261B), 5 μM Erlotinib (MedChemExpress, HY-50896), 5 μM Gefitinib (MedChemExpress, HY-50895), 5 μM Tinodasertib (MedChemExpress, HY-112424), 5 μM Tomiversotib (MedChemExpress, HY-100022), 5 μM WZ4002 (MedChemExpress, HY-12026), or 10 μM, 20 μM, 40 μM CP-24 for 24 h prior to sample collection.

Techniques: Control, Imaging

Journal: bioRxiv

Article Title: Prospective pan-cancer phosphoproteomics at clinical scale extends therapeutic options in precision oncology

doi: 10.64898/2026.07.08.737171

Figure Lengend Snippet: (A) Activity landscape in advanced chordoma patients (n=102 samples; 86 patients) for 10 RTKs. (only scores with n≥ 5 samples with TOPAS score ≥1 displayed). Samples are clustered by the respective RTK TOPAS score (≥1). (B) CellTiter-Glo proliferation assays of chordoma cell lines treated with afatinib (biological replicates = 2-3/cell line). Sensitive cell lines (EC50 <50nM) are colored in green and resistant cell lines (EC50>1000nM) in black. (C) Afatinib response in patient-derived xenograft (PDX) models (5-7 mice/arm). Graphs show the ratio of mean tumor volume in the therapy arm (20mg/kg afatinib) over the control arm at day of assessment (control arm >1500mm³ or at day 42). Models with a T/C ratio ≤ 0.5 are classified as responders and are colored in green. (D) Swarm plot illustrating EGFR TOPAS scores in the non-responder (n=9, black) and responder group (n=16, green) across chordoma cell lines (dot) and PDX models (rectangle). Differential abundance of MX1 in the EGFR TOPAS positive (z-score ≥1) responder and non-responder phenotypes. Differential abundance of TUSC3 in the EGFR TOPAS negative (z-score <1) responder and non-responder phenotypes. (E) Parallel coordinate plot using EGFR TOPAS socres and either MX1 protein expression (z-score) in case of EGFR TOPAS positivity or TUSC3 protein expression (z-score) in case of EGFR TOPAS negativity for chordoma model (cell line and PDX) stratification. Lines connecting coordinates are colored in green (responder phenotype) or black (non-responder phenotype). (F) Bar plot indicating the time under EGFR inhibition (erlotinib+bevacizumab, lapatinib or afatinib) in 7 patients. Patients with a therapy duration > 12 months (dashed grey line) are classified as responders and are colored in green. (G) Parallel coordinate plot using EGFR TOPAS scores and either MX1 protein expression (z-score) in case of EGFR TOPAS positivity or TUSC3 protein expression (z-score) in case of EGFR TOPAS negativity for chordoma patient stratification. Lines connecting coordinates for patients with clinical response are colored in green, for patients without response in black, and for patients without EGFR-therapy follow-up in grey.

Article Snippet: 10 mM afatinib in DMSO (MedChemExpress; Cat#: HY-10261) was diluted to 3 μM, the top concentration used in this assay, and then serially diluted by 1/3rd to 0.457 nM.

Techniques: Activity Assay, Derivative Assay, Control, Expressing, Inhibition, Clinical Proteomics

Journal: bioRxiv

Article Title: Prospective pan-cancer phosphoproteomics at clinical scale extends therapeutic options in precision oncology

doi: 10.64898/2026.07.08.737171

Figure Lengend Snippet: (A) Heatmap depicting EGFR pathway activity and genomic/transcriptomic alterations sorted by EGFR TOPAS kinase activity score from highest (left) to lowest (right) across all chordoma tumor specimen. Each column represents one patient (patient ID shown above). Rows show, from top to bottom: EGFR kinase activity score (TOPAS), EGFR protein abundance (z-score), EGFR mRNA expression (FPKM z-score), and somatic SNV, CNV, and gene fusion status. For quantitative rows, red indicates z-score ≥ 2, light red indicates z-score ≥ 1, light blue indicates z-score < 1, and grey indicates missing data. For genomic alteration rows, red indicates amplification (AMP); light blue indicates duplication (DUP), copy-number neutral (CNN), or deletion (DEL); dark grey indicates not determined (n.d.); light grey indicates not available (NA). (B) Tumor growth (volume) curves of PDX models treated with afatinib (20 mg/kg or 10 mg/kg daily, oral) in red or untreated in black for 42 days (or until the control group reached a mean tumor volume of 1,500 mm3), n=5-7 animals per group. (C,D) Volcano plot of differential expressed proteins in the EGFR-positive (C) or EGFR-negative (D) sensitive vs. resistant chordoma models (cell lines and PDX).

Article Snippet: 10 mM afatinib in DMSO (MedChemExpress; Cat#: HY-10261) was diluted to 3 μM, the top concentration used in this assay, and then serially diluted by 1/3rd to 0.457 nM.

Techniques: Activity Assay, Quantitative Proteomics, Expressing, Amplification, Control

Journal: Redox Biology

Article Title: C-terminal interleukin 1 alpha (IL-1α) overexpression drives EMT and a vulnerability to ferroptosis in HNSCC

doi: 10.1016/j.redox.2026.104172

Figure Lengend Snippet: IL-1α overexpression induces resistance to EGFR tyrosine kinase inhibitors. (A) Whole cell lysates were analyzed for EGFR and phosphorylated EGFR (pEGFR) expression by Western blot in control (CTL) and full-length (FL), N-terminal (NT) and C-terminal (CT) IL-1α overexpressed cells using α-Tubulin as a loading control, with quantification of protein expression shown in B and C. (D-G) Cell viability following 48 h treatment with Erlotinib (5 μM) (D), Afatinib (1 μM) (E), Osimertinib (1 μM) (F) and Silevertinib (1 μM) (G) was measured using MTT assays. Bars represent mean ± SEM from n = 3 independent experiments. ∗p < 0.05; ∗∗p < 0.01; ∗∗∗p < 0.001; ∗∗∗∗p < 0.0001.

Article Snippet: Afatinib, osimertinib and silivertinib (BDTX-1535) were from MedchemExpress (NJ, USA).

Techniques: Over Expression, Expressing, Western Blot, Control