ArticleOncotarget2015
Potent efficacy of metronomic topotecan and pazopanib combination therapy in preclinical models of primary or late stage metastatic triple-negative breast cancer.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
33 citing papers in PubMed, 62 citations in OpenAlex.
- Metronomic chemotherapy with oral vinorelbine (mVNR) and capecitabine (mCAPE) in advanced HER2-negative breast cancer patients: is it a way to optimize disease control? Final results of the VICTOR-2 study.Breast cancer research and treatment · 2016Trial
- Clinical utilities of platelet-derived growth factor signaling in breast cancer.Pharmacological research · 2026Review
- Algorithm-assisted individualized therapy design improves survival in a mouse model of triple-negative breast cancer.NPJ precision oncology · 2026Article
- Metronomic Chemotherapy in Breast Cancer: Unleashing the Potential of Combination Regimens.Cancer innovation · 2025Review
- Anlotinib in combination with metronomic chemotherapy in HER2-negative metastatic breast cancer: an observational and retrospective study.BMC cancer · 2025Observational
- Metronomic Chemotherapy in Elderly Patients.Current oncology reports · 2024Review
- Review
- Vessel co-option: a unique vascular-immune niche in liver cancer.Frontiers in oncology · 2024Review
- Computational simulations of tumor growth and treatment response: Benefits of high-frequency, low-dose drug regimens and concurrent vascular normalization.PLoS computational biology · 2023Article
- Implementing subtype-specific pre-clinical models of breast cancer to study pre-treatment aspirin effects.Cancer medicine · 2022Article
- Metronomic Chemotherapy for Metastatic Breast Cancer Treatment: Clinical and Preclinical Data between Lights and Shadows.Journal of clinical medicine · 2022Review
- Article
- Tumor vessel co-option: The past & the future.Frontiers in oncology · 2022Review
- Current Research Status of Metronomic Chemotherapy in Combination Treatment of Breast Cancer.Oncology research and treatment · 2022Review
- Metronomic chemotherapy (mCHT) in metastatic triple-negative breast cancer (TNBC) patients: results of the VICTOR-6 study.Breast cancer research and treatment · 2021Article
- Review
- Identification and Characterization of Key Differentially Expressed Genes Associated With Metronomic Dosing of Topotecan in Human Prostate Cancer.Frontiers in pharmacology · 2021Article
- Pharmacological effects of vinorelbine in combination with lenvatinib in anaplastic thyroid cancer.Pharmacological research · 2020Article
- A Pilot Study of Extended Adjuvant Therapy with Metronomic Docetaxel for Patients with Operable Triple-Negative Breast Cancer.Asian Pacific journal of cancer prevention : APJCP · 2020Article
- Vessel co-option in cancer.Nature reviews. Clinical oncology · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Metronomic chemotherapy has shown promising activity in numerous preclinical studies and also some phase II clinical studies involving various tumor types, and is currently undergoing phase III trial evaluation. Triple-negative breast cancer (TNBC) is an aggressive histological subtype with limited treatment options and very poor prognosis following progression after standard chemotherapeutic regimens. Herein, we evaluated the potential therapeutic impact and molecular mechanisms of topotecan administered in a continuous low-dose metronomic (LDM) manner, alone or in concurrent combination with pazopanib, an antiangiogenic tyrosine kinase inhibitor (TKI), in a triple-negative, primary and metastatic breast cancer orthotopic model; potential molecular mechanisms of efficacy were also studied, especially the impact of hypoxic conditions. The combination of metronomic topotecan and pazopanib significantly enhanced antitumor activity compared to monotherapy with either drug and prolonged survival, even in the advanced metastatic survival setting, with a marked decrease in tumor vascularity, proliferative index, and the induction of apoptosis. Significant changes in tumor angiogenesis, cancer cell proliferation, apoptosis, HIF1α levels, HIF-1 target genes and ABCG2 were found both in vitro and in tumor tissue. Notably, the pazopanib and metronomic topotecan combination treatment inhibited expression of HIF1α and ABCG2 genes in cells grown under hypoxic conditions, and this was associated with an increased intracellular concentration of the active form of topotecan. Our results suggest a potential novel therapeutic option for the treatment of metastatic triple-negative breast cancer patients.
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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.