nintedanib

Both in vitro and in vivo experiments have validated the therapeutic efficacy and molecular mechanisms of IL-11-neutralizing antibodies in pulmonary fibrosis, offering promising insights for future anti-fibrotic drug development. Abbreviations: IL-11, Interleukin-11; IPF, Idiopathic pulmonary fibrosis; TGF-β, Transforming growth factor-β; NOX4, NADPH oxidase-4; SASP, Senescence-associated secretory phenotype; ECM, Extracellular matrix; α-SMA, α-smooth muscle actin; STAT3, Signal transducer and activator of transcription 3; ERK, Extracellular regulated protein kinases; AKT, Protein kinase B; BLM, Bleomycin; WT, Wild-type; KO, Knockout; qRT-PCR, Quantitative real-time polymerase chain reaction; WB, Western blot; hAb, Humanized antibody; mAb, Monoclonal antibody; FVC, Forced vital capacity; CTGF, Connective tissue growth factor; PDGFR-α, Platelet-derived growth factor receptor-α; TNF-α, Tumor necrosis factor-α; Nrf2, NFE2-related factor 2; EMT, Epithelial-mesenchymal transition; HE, Hematoxylin and eosin; PVDF, Polyvinylidene fluoride; GAPDH, Glyceraldehyde-3-phosphate dehydrogenase; siRNA, Small interfering RNA; IL-6, Interleukin-6; MEK, Mitogen-Activated Protein Kinase Kinase; TIME, TGF-β1/IL-11/MEK/ERK; HRP, Horseradish Peroxidase; MLG, Mouse lung fibroblast cell line MLg; NCBI, National Center for Biotechnology Information; Bcl2, BCL2 apoptosis regulator; Bax, BCL2 Associated X, apoptosis regulator; MSC, Mesenchymal Stem Cell; RSK, p90 Ribosomal S6 Kinase; KD, Dissociation Constant; Nin, Nintedanib; CTL, Control; Eto, Etoposide; SA-β-Gal, Senescence-Associated β-Galactosidase.

Immunohistochemical analyses of pancreatic cancer tissues revealed high VEGFR2 expression in 83% (67/80) of samples, significantly exceeding the levels observed in normal pancreatic tissues. These results underscore VEGFR2 as a promising molecular target and propose a novel therapeutic avenue for KRAS-mutant cancers.

P2/3, N=16, Not yet recruiting, Celgene Corp.

P3, N=92, Recruiting, Juno Therapeutics, Inc., a Bristol-Myers Squibb Company | Initiation date: May 2026 --> Aug 2026

P=N/A, N=88, Terminated, Boehringer Ingelheim | Completed --> Terminated; Company decision

P=N/A, N=88, Completed, Boehringer Ingelheim | Active, not recruiting --> Completed

These findings were largely recapitulated in patient-derived PDA organoids, where GSTT1 and PROM1 co-expression predicted increased tumor sphere formation and enhanced response to the multi-kinase inhibitor Nintedanib. Together, these results identify a GSTT1 High CD133 High stem-like subpopulation in metastatic PDA and identify an FGFR-dependent signaling axis that sustains this state, representing a potential therapeutic vulnerability.

P=N/A, N=78, Completed, University of British Columbia | Trial completion date: Dec 2026 --> Aug 2025 | Trial primary completion date: Dec 2026 --> Aug 2025 | Recruiting --> Completed

P3, N=92, Recruiting, Juno Therapeutics, Inc., a Bristol-Myers Squibb Company | Not yet recruiting --> Recruiting

P1, N=57, Recruiting, Endeavor Biomedicines, Inc. | Not yet recruiting --> Recruiting

SB-525334 blocked all effects of TGF-β1, whereas nintedanib was more effective in counteracting the stimulatory effects of TGF-β1 on cell length and α-SMA. Interestingly, nintedanib, per se, evoked small but consistent effects opposite to those of TGF-β1. In conclusion, integrating these experimental approaches provides a powerful platform for detailed investigation of EMT mechanisms and for the identification of novel drug candidates that counteract EMT.

The histological and biochemical findings of the present study indicate that nintedanib is a promising pharmacological agent for the prevention of post-laminectomy epidural fibrosis. Further studies with larger sample sizes and interval assessments are needed to clarify the effects of different dosages.