ArticleNeoplasia (New York, N.Y.)2011
Tumors that acquire resistance to low-dose metronomic cyclophosphamide retain sensitivity to maximum tolerated dose cyclophosphamide.
Article in Neoplasia (New York, N.Y.), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed.
- Article
- Immunogenicity of an adjuvanted broadly active influenza vaccine in immunocompromised and diverse populations.Bioengineering & translational medicine · 2024Article
- Cyclic Metronomic Chemotherapy for Pediatric Tumors: Six Case Reports and a Review of the Literature.Journal of clinical medicine · 2022Review
- N-of-1 Healthcare: Challenges and Prospects for the Future of Personalized Medicine.Frontiers in digital health · 2022Article
- One method to establish Epstein-Barr virus-associated NK/T cell lymphoma mouse models.Journal of cellular and molecular medicine · 2019Article
- Resistance to metronomic chemotherapy and ways to overcome it.Cancer letters · 2017Review
- Thrombospondin-targeting TAX2 peptide impairs tumor growth in preclinical mouse models of childhood neuroblastoma.Pediatric research · 2017Article
- Is There an Opportunity for Current Chemotherapeutics to Up-regulate MIC-A/B Ligands?Frontiers in pharmacology · 2017Article
- Impact of CTLA-4 blockade in conjunction with metronomic chemotherapy on preclinical breast cancer growth.British journal of cancer · 2017Article
- Limiting the development of anti-cancer drug resistance in a spatial model of micrometastases.Mathematical biosciences and engineering : MBE · 2016Article
- Metronomic methotrexate and cyclophosphamide after carboplatin included adjuvant chemotherapy in triple negative breast cancer: a phase III study.Annals of translational medicine · 2015Article
- Metronomic cyclophosphamide schedule-dependence of innate immune cell recruitment and tumor regression in an implanted glioma model.Cancer letters · 2014Article
- Analysis of acquired resistance to metronomic oral topotecan chemotherapy plus pazopanib after prolonged preclinical potent responsiveness in advanced ovarian cancer.Angiogenesis · 2014Article
- Metronomics: towards personalized chemotherapy?Nature reviews. Clinical oncology · 2014Review
- Pigment epithelium-derived factor expression prolongs survival and enhances the cytotoxicity of low-dose chemotherapy in castration-refractory prostate cancer.Cell death & disease · 2014Article
- Treatment-induced host-mediated mechanisms reducing the efficacy of antitumor therapies.Oncogene · 2014Review
- Preclinical analysis of resistance and cross-resistance to low-dose metronomic chemotherapy.Investigational new drugs · 2014Article
- Cancer subclonal genetic architecture as a key to personalized medicine.Neoplasia (New York, N.Y.) · 2013Article
- VEGF-A polymorphisms predict progression-free survival among advanced castration-resistant prostate cancer patients treated with metronomic cyclophosphamide.British journal of cancer · 2013Article
- Tumor dynamics in response to antiangiogenic therapy with oral metronomic topotecan and pazopanib in neuroblastoma xenografts.Translational oncology · 2013Article
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Authors and funding
7 authors.
Funding
Abstract
Low-dose metronomic (LDM) chemotherapy is emerging as an alternative or supplemental dosing strategy to conventional maximum tolerated dose (MTD) chemotherapy. It is characterized primarily, but not exclusively, by antiangiogenic mechanisms of action and the absence of high-grade adverse effects commonly seen with MTD chemotherapy. However, similar to other anticancer therapies, inherent resistance to LDM chemotherapy is common. Moreover, even tumors that initially respond to metronomic regimens eventually develop resistance through mechanisms that are as yet unknown. Thus, we have developed in vivo models of PC-3 human prostate cancer cells resistant to extended LDM cyclophosphamide therapy. Such PC-3 variants show stable resistance to LDM cyclophosphamide in vivo yet retain in vitro sensitivity to 4-hydroperoxy-cyclophosphamide (precursor of the active cyclophosphamide metabolite 4-hydroxy-cyclophosphamide) and other chemotherapeutic agents, namely, docetaxel and doxorubicin. Moreover, LDM cyclophosphamide-resistant PC-3 variants remain sensitive to MTD cyclophosphamide therapy in vivo. Conversely, PC-3 variants made resistant in vivo to MTD cyclophosphamide show varying levels of resistance to metronomic cyclophosphamide when grown in mice. These results and additional studies of variants of the breast cancer cell line MDA-MB-231 suggest that resistance to LDM cyclophosphamide is a distinct phenomenon from resistance to MTD cyclophosphamide and that LDM cyclophosphamide administration does not select for MTD chemotherapy resistance. As such, our findings have various implications for the clinical use of metronomic chemotherapy.
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