ArticleCancer letters2016
Combined targeting of TGF-β, EGFR and HER2 suppresses lymphangiogenesis and metastasis in a pancreatic cancer model.
Article in Cancer letters, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.
- Polymorphisms within autophagy-related genes as susceptibility biomarkers for pancreatic cancer: A meta-analysis of three large European cohorts and functional characterization.International journal of cancer · 2025Pooled it
- Pancreatic Lymphatics in Health and Disease: Evolution, Embryology, and Neural Control.Lymphatics · 2026Article
- Molecular Mechanisms of Thyroid Hormone Signaling in Thyroid Cancer: Oncogenesis, Progression, and Therapeutic Implications.Biomedicines · 2025Review
- Lapatinib ameliorates skin fibrosis by inhibiting TGF-β1/Smad and non-Smad signaling pathway.Scientific reports · 2025Article
- Genome-Wide Characterization of Fennel (Anethum foeniculum) MiRNome and Identification of its Potential Targets in Homo sapiens and Arabidopsis thaliana: An Inter and Intra-species Computational Scrutiny.Biochemical genetics · 2024Article
- Single-Nuclei Characterization of Lacrimal Gland in Scopolamine-Induced Dry Eye Disease.Investigative ophthalmology & visual science · 2024Article
- Lymphatic vessel: origin, heterogeneity, biological functions, and therapeutic targets.Signal transduction and targeted therapy · 2024Review
- Physiological and pathological roles of Hic‑5 in several organs (Review).International journal of molecular medicine · 2022Review
- Pancreatic Cancer Cell-Derived Exosomes Promote Lymphangiogenesis by Downregulating ABHD11-AS1 Expression.Cancers · 2022Article
- Implication of ERBB2 as a Predictive Tool for Survival in Patients with Pancreatic Cancer in Histological Studies.Current oncology (Toronto, Ont.) · 2022Article
- The lymphatic vasculature: An active and dynamic player in cancer progression.Medicinal research reviews · 2022Review
- Kuoxin Decoction promotes lymphangiogenesis in zebrafish andFrontiers in pharmacology · 2022Article
- TGF-β Signaling in Liver, Pancreas, and Gastrointestinal Diseases and Cancer.Gastroenterology · 2021Review
- circEHBP1 promotes lymphangiogenesis and lymphatic metastasis of bladder cancer via miR-130a-3p/TGFβR1/VEGF-D signaling.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- TGFB1/INHBA Homodimer/Nodal-SMAD2/3 Signaling Network: A Pivotal Molecular Target in PDAC Treatment.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Review
- Article
- Valproic acid exhibits anti-tumor activity selectively against EGFR/ErbB2/ErbB3-coexpressing pancreatic cancer via induction of ErbB family members-targeting microRNAs.Journal of experimental & clinical cancer research : CR · 2019Article
- The Contribution of the Immune System in Bone Metastasis Pathogenesis.International journal of molecular sciences · 2019Review
- Internal enhancement of DNA damage by a novel bispecific antibody-drug conjugate-like therapeutics via blockage of mTOR and PD-L1 signal pathways in pancreatic cancer.Cancer medicine · 2019Article
- Tumor-Associated Lymphatic Vessel Features and Immunomodulatory Functions.Frontiers in immunology · 2019Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Pancreatic ductal adenocarcinomas (PDACs) are aggressive with frequent lymphatic spread. By analysis of data from The Cancer Genome Atlas, we determined that ~35% of PDACs have a pro-angiogenic gene signature. We now show that the same PDACs exhibit increased expression of lymphangiogenic genes and lymphatic endothelial cell (LEC) markers, and that LEC abundance in human PDACs correlates with endothelial cell microvessel density. Lymphangiogenic genes and LECs are also elevated in murine PDACs arising in the KRC (mutated Kras; deleted RB) and KIC (mutated Kras; deleted INK4a) genetic models. Moreover, pancreatic cancer cells (PCCs) derived from KRC tumors express and secrete high levels of lymphangiogenic factors, including the EGF receptor ligand, amphiregulin. Importantly, TGF-β1 increases lymphangiogenic genes and amphiregulin expression in KRC PCCs but not in murine PCCs that lack SMAD4, and combinatorial targeting of the TGF-β type I receptor (TβRI) with LY2157299 and EGFR/HER2 with lapatinib suppresses tumor growth and metastasis in a syngeneic orthotopic model, and attenuates tumor lymphangiogenesis and angiogenesis while reducing lymphangiogenic genes and amphiregulin and enhancing apoptosis. Therefore, this combination could be beneficial in PDACs with lymphangiogenic or angiogenic gene signatures.
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What OpenQuestion holds
Registered trials
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.