ArticleCancer research2014
Paclitaxel therapy promotes breast cancer metastasis in a TLR4-dependent manner.
Article in Cancer research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 135 papers, 1 of them a synthesis that pooled it.
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Who cites it
135 citing papers in PubMed, 1 synthesis or guideline pooled it, 229 citations in OpenAlex.
- Pooled it
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- 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
- Mechanisms of Paclitaxel Resistance: Recent Advances and Future Perspectives.International journal of molecular sciences · 2026Review
- Localization and Biological Activities of Bioflavonoids fromInternational journal of molecular sciences · 2026Article
- Fusobacterium nucleatum in cancer: Interactions with microbiota, tumour colonisation and cancer progression.Clinical and translational medicine · 2026Review
- Taxane chemotherapy promotes response to TIM-3 checkpoint blockade via STING-mediated ER stress and HMGB1 secretion.Cell reports. Medicine · 2026Article
- Integrative transcriptomic analysis reveals novel targets for personalized medicine across seven metastatic breast cancer subtypes.Scientific reports · 2026Article
- Tumor-Associated Macrophages (TAMs) in Cancer: Functional Programs, Metastatic Mechanisms, and Therapeutic Targeting.Cancers · 2026Review
- 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
- Crocetin Impairs the Cytochrome P450 Epoxygenase Pathway toward Potentiating the Therapeutic Efficacy of Paclitaxel in Metastatic Breast Cancer.ACS omega · 2025Article
- Mechanisms and Therapeutic Strategies for Minority Cell-Induced Paclitaxel Resistance and Tumor Progression Mediated by Mechanical Forces.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Bone Marrow Myeloid-Lymphatic Progenitors Expand Tumor Lymphatic Vasculature Through Cell Fusion.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
- Fruquintinib saddles tumor immune tolerance by curbing pro-tumoral immature myeloid cell populations.Frontiers in immunology · 2025Article
- YAP/TEAD involvement in resistance to paclitaxel chemotherapy in lung cancer.Molecular and cellular biochemistry · 2025Article
- The multiple biological activities of hyperoside: from molecular mechanisms to therapeutic perspectives in neoplastic and non-neoplastic diseases.Frontiers in pharmacology · 2025Review
- Novel Inhibition of Central Carbon Metabolism Pathways by Rac and CDC42 inhibitor MBQ167 and Paclitaxel.Molecular cancer therapeutics · 2024Article
75 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Emerging evidence suggests that cytotoxic therapy may actually promote drug resistance and metastasis while inhibiting the growth of primary tumors. Work in preclinical models of breast cancer has shown that acquired chemoresistance to the widely used drug paclitaxel can be mediated by activation of the Toll-like receptor TLR4 in cancer cells. In this study, we determined the prometastatic effects of tumor-expressed TLR4 and paclitaxel therapy and investigated the mechanisms mediating these effects. While paclitaxel treatment was largely efficacious in inhibiting TLR4-negative tumors, it significantly increased the incidence and burden of pulmonary and lymphatic metastasis by TLR4-positive tumors. TLR4 activation by paclitaxel strongly increased the expression of inflammatory mediators, not only locally in the primary tumor microenvironment but also systemically in the blood, lymph nodes, spleen, bone marrow, and lungs. These proinflammatory changes promoted the outgrowth of Ly6C(+) and Ly6G(+) myeloid progenitor cells and their mobilization to tumors, where they increased blood vessel formation but not invasion of these vessels. In contrast, paclitaxel-mediated activation of TLR4-positive tumors induced de novo generation of deep intratumoral lymphatic vessels that were highly permissive to invasion by malignant cells. These results suggest that paclitaxel therapy of patients with TLR4-expressing tumors may activate systemic inflammatory circuits that promote angiogenesis, lymphangiogenesis, and metastasis, both at local sites and premetastatic niches where invasion occurs in distal organs. Taken together, our findings suggest that efforts to target TLR4 on tumor cells may simultaneously quell local and systemic inflammatory pathways that promote malignant progression, with implications for how to prevent tumor recurrence and the establishment of metastatic lesions, either during chemotherapy or after it is completed.
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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.