ArticleNature communications2022
An EGFR/HER2-targeted conjugate sensitizes gemcitabine-sensitive and resistant pancreatic cancer through different SMAD4-mediated mechanisms.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Acquired resistance to the RAS(ON) multi-selective inhibitor daraxonrasib guides rational combination therapy strategies in pancreatic cancer.Nature medicine · 2026Trial
- Targeted Cepharanthine-Mediated Dual-Pathway Inhibition Sensitizes Pancreatic Cancer to Gemcitabine.Life (Basel, Switzerland) · 2026Article
- MEK inhibitor-based genomically matched combinatorial targeted therapies in metastatic pancreatic adenocarcinoma with KRAS alterations.The oncologist · 2026Observational
- Hui-Xiang Decoction Against Pancreatic Cancer by Regulating AKT and Activating the Hippo Signaling Pathway.Chemistry & biodiversity · 2026Article
- Cathepsin K Alleviates Liver Fibrosis by Inhibiting the TGF-β/Smad Signaling Pathway and Inducing Hepatic Stellate Cell Apoptosis.Journal of clinical and translational hepatology · 2026Article
- USP10 promotes cell proliferation and gemcitabine resistance in pancreatic cancer by the regulation of IGF2BP3-STEAP3.Oncogene · 2026Article
- Network pharmacology and experimental study on the inhibition of glycolysis by amentoflavone in pancreatic cancer.Discover oncology · 2025Article
- Engineering exosome membrane disguised thermal responsive system for targeted drug delivery and controlled release across the blood-brain barrier.Materials today. Bio · 2025Article
- Rational Design of Biocompatible Ir(III) Photosensitizer to Overcome Drug-Resistant Cancer via Oxidative Autophagy Inhibition.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- A novel gemcitabine analog as a potential anticancer agent: synthesis andAmerican journal of cancer research · 2025Article
- Clinical application and drug resistance mechanism of gemcitabine.Frontiers in cell and developmental biology · 2025Review
- PHF12 regulates HDAC1 to promote tumorigenesis via EGFR/AKT signaling pathway in non-small cell lung cancer.Journal of translational medicine · 2024Article
- Induced dual-target rebalance simultaneously enhances efficient therapeutical efficacy in tumors.Cell death discovery · 2024Article
- Review
- SMAD4 endows TGF-β1-induced highly invasive tumor cells with ferroptosis vulnerability in pancreatic cancer.Acta pharmacologica Sinica · 2024Article
- Improved Antitumor Efficiency ofInternational journal of nanomedicine · 2024Article
- Advanced renal pelvis carcinoma patient with an ERBB2 insertion mutation: a case report.The Journal of international medical research · 2023Article
- CircLDLRAD3 inhibits Oral squamous cell carcinoma progression by regulating miR-558/Smad4/TGF-β.Journal of cellular and molecular medicine · 2023Article
- SMAD Proteins in TGF-β Signalling Pathway in Cancer: Regulatory Mechanisms and Clinical Applications.Diagnostics (Basel, Switzerland) · 2023Review
- Exploring the therapeutic mechanisms of Gleditsiae Spina acting on pancreatic cancerRSC advances · 2023Article
Corrections and comments
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Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chemoresistance limits its clinical implementation for pancreatic ductal adenocarcinoma (PDAC). We previously generated an EGFR/HER2 targeted conjugate, dual-targeting ligand-based lidamycin (DTLL), which shows a highly potent antitumor effect. To overcome chemoresistance in PDAC, we aim to study DTLL efficacy when combined with gemcitabine and explore its mechanisms of action. DTLL in combination with gemcitabine show a superior inhibitory effect on the growth of gemcitabine-resistant/sensitive tumors. DTLL sensitizes gemcitabine efficacy via distinct action mechanisms mediated by mothers against decapentaplegic homolog 4 (SMAD4). It not only prevents neoplastic proliferation via ATK/mTOR blockade and NF-κB impaired function in SMAD4-sufficient PDACs, but also restores SMAD4 bioactivity to trigger downstream NF-κB-regulated signaling in SMAD4-deficient tumors and to overcome chemoresistance. DTLL seems to act as a SMAD4 module that normalizes its function in PDAC, having a synergistic effect in combination with gemcitabine. Our findings provide insight into a rational SMAD4-directed precision therapy in PDAC.
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