ArticleOncotarget2016
Zoledronic acid-encapsulating self-assembling nanoparticles and doxorubicin: a combinatorial approach to overcome simultaneously chemoresistance and immunoresistance in breast tumors.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Cholesterol and Its Derivatives: Multifaceted Players in Breast Cancer Progression.Frontiers in oncology · 2022Pooled it
- Clinical insight-driven micron-sized cholesterol oxidation platform for membrane lipid therapy of advanced ovarian cancer.Journal of nanobiotechnology · 2025Article
- The signature of extracellular vesicles in hypoxic breast cancer and their therapeutic engineering.Cell communication and signaling : CCS · 2024Review
- Comprehensive review of drug-mediated ICD inhibition of breast cancer: mechanism, status, and prospects.Clinical and experimental medicine · 2024Review
- TFEB controls sensitivity to chemotherapy and immuno-killing in non-small cell lung cancer.Journal of experimental & clinical cancer research : CR · 2024Article
- Engineering nanomedicines for immunogenic eradication of cancer cells: Recent trends and synergistic approaches.Acta pharmaceutica Sinica. B · 2024Review
- Immunotherapy Innovations in the Fight against Osteosarcoma: Emerging Strategies and Promising Progress.Pharmaceutics · 2024Review
- Regulating Cholesterol in Tumorigenesis: A Novel Paradigm for Tumor Nanotherapeutics.International journal of nanomedicine · 2024Review
- Harnessing Nanomedicine to Potentiate the Chemo-Immunotherapeutic Effects of Doxorubicin and Alendronate Co-Encapsulated in Pegylated Liposomes.Pharmaceutics · 2023Article
- β-Sitosterol as a Promising Anticancer Agent for Chemoprevention and Chemotherapy: Mechanisms of Action and Future Prospects.Advances in nutrition (Bethesda, Md.) · 2023Review
- Strategies to Overcome Resistance to Immune-Based Therapies in Osteosarcoma.International journal of molecular sciences · 2023Review
- ThPOK inhibits the immune escape of gastric cancer cells by inducing STPG1 to inactivate the ERK pathway.BMC immunology · 2022Article
- Nanomedicine as a Promising Tool to Overcome Immune Escape in Breast Cancer.Pharmaceutics · 2022Review
- The MEK/ERK Network as a Therapeutic Target in Human Cancer.Molecular cancer research : MCR · 2021Review
- Hypoxia, endoplasmic reticulum stress and chemoresistance: dangerous liaisons.Journal of experimental & clinical cancer research : CR · 2021Review
- Mechanisms of Resistance to Chemotherapy in Breast Cancer and Possible Targets in Drug Delivery Systems.Pharmaceutics · 2020Review
- Various pathways of zoledronic acid against osteoclasts and bone cancer metastasis: a brief review.BMC cancer · 2020Review
- Tumor-associated macrophages: Role in the pathological process of tumorigenesis and prospective therapeutic use (Review).Biomedical reports · 2020Review
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Corrections and comments
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Authors and funding
12 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The resistance to chemotherapy and the tumor escape from host immunosurveillance are the main causes of the failure of anthracycline-based regimens in breast cancer, where an effective chemo-immunosensitizing strategy is lacking.The clinically used aminobisphosphonate zoledronic acid (ZA) reverses chemoresistance and immunoresistance in vitro. Previously we developed a nanoparticle-based zoledronic acid-containing formulation (NZ) that allowed a higher intratumor delivery of the drug compared with free ZA in vivo. We tested its efficacy in combination with doxorubicin in breast tumors refractory to chemotherapy and immune system recognition as a new combinatorial approach to produce chemo- and immunosensitization.NZ reduced the IC50 of doxorubicin in human and murine chemoresistant breast cancer cells and restored the doxorubicin efficacy against chemo-immunoresistant tumors implanted in immunocompetent mice. By reducing the metabolic flux through the mevalonate pathway, NZ lowered the activity of Ras/ERK1/2/HIF-1α axis and the expression of P-glycoprotein, decreased the glycolysis and the mitochondrial respiratory chain, induced a cytochrome c/caspase 9/caspase 3-dependent apoptosis, thus restoring the direct cytotoxic effects of doxorubicin on tumor cell. Moreover, NZ restored the doxorubicin-induced immunogenic cell death and reversed the tumor-induced immunosuppression due to the production of kynurenine, by inhibiting the STAT3/indoleamine 2,3 dioxygenase axis. These events increased the number of dendritic cells and decreased the number of immunosuppressive T-regulatory cells infiltrating the tumors.Our work proposes the use of nanoparticle encapsulating zoledronic acid as an effective tool overcoming at the same time chemoresistance and immunoresistance in breast tumors, thanks to the effects exerted on tumor cell and tumor-infiltrating immune cells.
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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.