ArticleMolecular cancer therapeutics2013
TLR4 is a novel determinant of the response to paclitaxel in breast cancer.
Article in Molecular cancer therapeutics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers.
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Who cites it
100 citing papers in PubMed, 163 citations in OpenAlex.
- A Phase Ib/II Study of the JAK1 Inhibitor, Itacitinib, plusThe oncologist · 2019Trial
- Dysregulation of the TLR4/MYD88 Signaling Pathway in Egyptian Females with Breast Cancer: Implications for Tumor Progression.Molecular biology reports · 2026Article
- Uncoupling Type I Interferon Benefits From Inflammatory Toxicity: Transformer-Prioritized Precision Agonists for Potent and Safer Cancer Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A CXCR4/PD-L1 Bispecific Nanobody Engineered for Tumor Microenvironment Retention Mediates Sustained Synergy with Chemotherapy via Remodeling Immunity in TNBC.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Zinc Complexation Overcomes the Context-Dependent Metabolic Effects of Curcumin in TNBC: Molecular Insights from TLR4/MD-2 Targeting.Current issues in molecular biology · 2026Article
- Fusobacterium nucleatum in cancer: Interactions with microbiota, tumour colonisation and cancer progression.Clinical and translational medicine · 2026Review
- Gut Microbiota and Extraintestinal Cancers: Mechanistic Insights and Microbiome-Targeted Interventions.JGH open : an open access journal of gastroenterology and hepatology · 2026Review
- Induction of Human β-Defensin-2 by VaginalOpen forum infectious diseases · 2026Article
- Protective effect of hesperetin against myelosuppression and splenic inflammation via modulating TLR4/MYD88/NF-κB signaling: molecular docking and experimental validation.Frontiers in pharmacology · 2026Article
- Δ133p53 isoform enhances TLR4 function to promote tumor growth.Carcinogenesis · 2025Article
- Bacterial Infections and Their Cell Wall Ligands Differentially Modulate Doxorubicin Sensitivity in Triple-Negative Breast Cancer Cells.Microorganisms · 2025Article
- Natural compounds and programmed necrosis: pioneering a new frontier in cancer treatments.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Astrocyte elevated gene-1 (AEG-1) in myeloid cells is a key driver for the development of chemotherapy-induced peripheral neuropathy.Brain, behavior, and immunity · 2025Article
- Clinical Significance and Prognostic Value of TLR4 and AGER in Inflammatory Breast Cancer.Cancers · 2025Article
- The role of TLR-4 in chemoresistance of cancer.Discover oncology · 2025Review
- Paclitaxel, interferons and functional reprogramming of tumor-associated macrophages in optimized chemo-immunotherapy.Journal for immunotherapy of cancer · 2025Review
- S100A8 as a potential therapeutic target for cancer metastasis.Cancer science · 2025Review
- Effects of gut microbiota in breast cancer.Frontiers in oncology · 2025Review
- Expression of toll-like receptors and inflammatory mediators in primary human glioma cells (low- and high-grade) compared to primary cells from epileptic human brain.Iranian journal of basic medical sciences · 2025Article
- Multi-Drug Resistance and Breast Cancer Progression via Toll-Like Receptors (TLRs) Signaling.Cell biochemistry and biophysics · 2024Review
40 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Overexpression of Toll-like receptor-4 (TLR4) in human tumors often correlates with chemoresistance and metastasis. We found that TLR4 is overexpressed in the majority of clinical breast cancer samples and in 68% of the examined breast cancer lines. TLR4 is activated by lipopolysaccharide (LPS) and other ligands including the widely used drug paclitaxel. LPS is frequently used to show a tumor-promoting role of TLR4 although this bacterial component is unlikely to be found in the breast cancer environment. We reasoned that paclitaxel-dependent activation of TLR4 is more relevant to breast cancer chemoresistance that could be mediated by activation of the NF-κB pathway leading to upregulation of prosurvival genes. To test this hypothesis, we correlated TLR4 expression with resistance to paclitaxel in two modified breast cancer lines with either depleted or overexpressed TLR4 protein. Depletion of TLR4 in naturally overexpressing MDA-MB-231 cells downregulated prosurvival genes concomitant with 2- to 3-fold reduced IC(50) to paclitaxel in vitro and a 6-fold decrease in recurrence rate in vivo. Conversely, TLR4 overexpression in a negative cell line HCC1806 significantly increased expression of inflammatory and prosurvival genes along with a 3-fold increase of IC(50) to paclitaxel in vitro and enhanced tumor resistance to paclitaxel therapy in vivo. Importantly, both tumor models showed that many paclitaxel-upregulated inflammatory cytokines were coinduced with their receptors suggesting that this therapy induces autocrine tumor-promoting loops. Collectively, these results show that paclitaxel not only kills tumor cells but also enhances their survival by activating TLR4 pathway. These findings suggest that blocking TLR4 could significantly improve response to paclitaxel therapy.
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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.