ArticleCellular oncology (Dordrecht, Netherlands)2015
Anti-tumor activity of the TGF-β receptor kinase inhibitor galunisertib (LY2157299 monohydrate) in patient-derived tumor xenografts.
Article in Cellular oncology (Dordrecht, Netherlands), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 42 citations in OpenAlex.
- Loss of ALK4 promotes cancer progression through regulating TGF-β receptor N-glycosylation.Nature communications · 2025Article
- Epithelial-mesenchymal transition (EMT) and its role in acquired epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) chemoresistance in non-small cell lung cancer (NSCLC).Cancer pathogenesis and therapy · 2025Review
- Therapeutic targeting of TGF-β in lung cancer.The FEBS journal · 2025Review
- The Function of the TGFβ Signaling Pathway in Connective Tissue Diseases: From Biology to Clinical Application.Journal of inflammation research · 2025Review
- Review
- Pharmacogenomics characterization of the MDM2 inhibitor MI-773 reveals candidate tumours and predictive biomarkers.NPJ precision oncology · 2021Article
- Role of TGF-β in pancreatic ductal adenocarcinoma progression and PD-L1 expression.Cellular oncology (Dordrecht, Netherlands) · 2021Article
- Immune-Checkpoint Inhibitors Combinations in Metastatic NSCLC: New Options on the Horizon?ImmunoTargets and therapy · 2021Review
- TGFβ-Directed Therapeutics: 2020.Pharmacology & therapeutics · 2021Review
- Evaluation of molecular subtypes and clonal selection during establishment of patient-derived tumor xenografts from gastric adenocarcinoma.Communications biology · 2020Article
- Bone Marrow-Derived Myofibroblasts Promote Gastric Cancer Metastasis by Activating TGF-β1 and IL-6/STAT3 Signalling Loop.OncoTargets and therapy · 2020Article
- CAR T cells for brain tumors: Lessons learned and road ahead.Immunological reviews · 2019Review
- Combination Therapy of TGF-β Blockade and Commensal-derived Probiotics Provides Enhanced Antitumor Immune Response and Tumor Suppression.Theranostics · 2019Article
- Review
- LY2157299 Monohydrate, a TGF-βR1 Inhibitor, Suppresses Tumor Growth and Ascites Development in Ovarian Cancer.Cancers · 2018Article
- Evaluating the antifibrotic potency of galunisertib in a human ex vivo model of liver fibrosis.British journal of pharmacology · 2017Article
- Transforming growth factor-β: A therapeutic target for cancer.Human vaccines & immunotherapeutics · 2017Review
- The TGF-β pathway: a pharmacological target in hepatocellular carcinoma?Hepatic oncology · 2017Article
- TGFβR1 Blockade with Galunisertib (LY2157299) Enhances Anti-Neuroblastoma Activity of the Anti-GD2 Antibody Dinutuximab (ch14.18) with Natural Killer Cells.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Article
- Down-regulation of osteopontin mediates a novel mechanism underlying the cytostatic activity of TGF-β.Cellular oncology (Dordrecht, Netherlands) · 2016Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeThe transforming growth factor-beta (TGF-β) signaling pathway is known to play a critical role in promoting tumor growth. Consequently, blocking this pathway has been found to inhibit tumor growth. In order to achieve an optimal anti-tumor effect, however, it remains to be established whether blocking the TGF-β signaling pathway alone is sufficient, or whether the tumor microenvironment plays an additional, possibly synergistic, role.
methodsTo investigate the relevance of blocking TGF-β signaling in tumor cells within the context of their respective tissue microenvironments, we treated a panel of patient-derived xenografts (PDX) with the selective TGF-β receptor kinase inhibitor LY2157299 monohydrate (galunisertib) and assessed both the in vitro and in vivo effects.
resultsGalunisertib was found to inhibit the growth in an in vitro clonogenic assay in 6.3% (5/79) of the examined PDX. Evaluation of the expression profiles of a number of genes, representing both canonical and non-canonical TGF-β signaling pathways, revealed that most PDX exhibited expression changes affecting TGF-β downstream signaling. Next, we subjected 13 of the PDX to an in vivo assessment and, by doing so, observed distinct response patterns. These results suggest that, next to intrinsic, also extrinsic or microenvironmental factors can affect galunisertib response. pSMAD2 protein expression and TGF-βRI mRNA expression levels were found to correlate with the in vivo galunisertib effects.
conclusionsFrom our data we conclude that intrinsic, tumor-dependent TGF-β signaling does not fully explain the anti-tumor effect of galunisertib. Hence, in vivo xenograft models may be more appropriate than in vitro clonogenic assays to assess the anti-tumor activity of TGF-β inhibitors such as galunisertib.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.