ArticleCell death & disease2023
Combination treatment of T1-44, a PRMT5 inhibitor with Vactosertib, an inhibitor of TGF-β signaling, inhibits invasion and prolongs survival in a mouse model of pancreatic tumors.
Article in Cell death & disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- Improving Outcomes in Pancreatic Adenocarcinoma: A Systematic Review of Immunotherapy in Multimodal Treatment.Medicina (Kaunas, Lithuania) · 2025Pooled it
- 3D-embedding of human gingiva-derived mesenchymal stromal cells in "VitroGelBMC oral health · 2026Article
- Recent advances in TGF-β signaling: insights into regulation, pathophysiological function, and clinical translation.Cell regeneration (London, England) · 2026Article
- TGFβ Blockade by Inhibition of Enolase-1-Mediated Plasmin Targets Tumor-Associated Macrophages in Pancreatic Ductal Adenocarcinoma.Oncology research · 2026Article
- Activin A-Activated ALK4 Induces Pathogenic Th17-Involved Endothelial-Mesenchymal Transition in Systemic Lupus Erythematosus-Associated Pulmonary Arterial Hypertension.Arthritis & rheumatology (Hoboken, N.J.) · 2025Article
- PRMT5 Promotes Pancreatic Cancer Tumorigenesis via Positive PRMT5/C-Myc Feedback Loop.MedComm · 2025Article
- PRMT5 inhibitors: Therapeutic potential in pancreatic cancer.Translational oncology · 2025Review
- Pancreatic cancer subtyping - the keystone of precision treatment.Frontiers in immunology · 2025Review
- Innovative Nanomedicine Delivery: Targeting Tumor Microenvironment to Defeat Drug Resistance.Pharmaceutics · 2024Review
- ADAMTS16 drives epithelial-mesenchymal transition and metastasis through a feedback loop upon TGF-β1 activation in lung adenocarcinoma.Cell death & disease · 2024Article
- The TGFβ type I receptor kinase inhibitor vactosertib in combination with pomalidomide in relapsed/refractory multiple myeloma: a phase 1b trial.Nature communications · 2024Article
- Advances and Challenges in Targeting TGF-β Isoforms for Therapeutic Intervention of Cancer: A Mechanism-Based Perspective.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Small-molecule agents for cancer immunotherapy.Acta pharmaceutica Sinica. B · 2024Review
- The TGF-β superfamily as potential therapeutic targets in pancreatic cancer.Frontiers in oncology · 2024Review
- Unleashing the Power of Synthetic Lethality: Augmenting Treatment Efficacy through Synergistic Integration with Chemotherapy Drugs.Pharmaceutics · 2023Review
- Therapeutic Advantage of Targeting PRMT5 in Combination with Chemotherapies or EGFR/HER2 Inhibitors in Triple-Negative Breast Cancers.Breast cancer (Dove Medical Press) · 2023Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is the most lethal type of cancer and the third leading cause of cancer death with the lowest 5-year survival rate. Heterogeneity, difficulty in diagnosis, and rapid metastatic progression are the causes of high mortality in pancreatic cancer. Recent studies have shown that Protein arginine methyltransferase 5 (PRMT5) is overexpressed in pancreatic cancers, and these patients have a worse prognosis. Recently, PRMT5 as an anti-cancer target has gained considerable interest. In this study, we investigated whether inhibition of PRMT5 activity was synergistic with blockade of TGF-β1 signaling, which plays an important role in the construction of the desmoplastic matrix in pancreatic cancer and induces therapeutic vulnerability. Compared with T1-44, a selective inhibitor of PRMT5 activity, the combination of T1-44 with the TGF-β1 signaling inhibitor Vactosertib significantly reduced tumor size and surrounding tissue invasion and significantly improved long-term survival. RNA sequencing analysis of mouse tumors revealed that the combination of T1-44 and Vactosertib significantly altered the expression of genes involved in cancer progression, such as cell migration, extracellular matrix, and apoptotic processes. In particular, the expression of Btg2, known as a tumor suppressor factor in various cancers, was markedly induced by combination treatment. Ectopic overexpression of Btg2 inhibited the EMT response, blocking cell migration, and promoted cancer cell death. These data demonstrate that the combination therapy of T1-44 with Vactosertib is synergistic for pancreatic cancer, suggesting that this novel combination therapy has value in the treatment strategy of patients with pancreatic cancer.
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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 Socratic graph.