title: Metronomic chemotherapy: A potent macerator of cancer by inducing angiogenesis suppression and antitumor immune activation.
abstract: Metronomic chemotherapy is a low dosing treatment strategy that attracts growing scientific and clinical interest. It refers to dense and uninterrupted administration of low doses of chemotherapeutic agents (without prolonged drug free intervals) over extended periods of time. Cancer chemotherapy is conventionally given in cycles of maximum tolerated doses (MTD) with the aim of inducing maximum cancer cell apoptosis. In contrast, the primary target of metronomic chemotherapy is the tumor's neovasculature. This is relevant to the emerging concept that tumors exist in a complex microenvironment of cancer cells, stromal cells and supporting vessels. In addition to its anti-angiogenetic properties, metronomic chemotherapy halts tumor growth by activating anti-tumor immunity, thus decreasing the acquired resistance to conventional chemotherapy. Herein, we present a review of the literature that provides a scientific basis for the merits of chemotherapy when administered on a metronomic schedule.
authors.affiliation: Department of Medical Oncology, University Hospital of Evros, Alexandroupolis, 68 100, Greece. Electronic address: eirinibiziota@gmail.com.
authors.forename: Eirini
authors.initials: E
authors.lastname: Biziota
authors.affiliation: Department of Pharmacology, Faculty of Medicine, School of Life Sciences, University of Ioannina, Ioannina, 451 10, Greece. Electronic address: leo.mavroidis@gmail.com.
authors.forename: Leonidas
authors.initials: L
authors.lastname: Mavroeidis
authors.affiliation: Department of Haematology, University Hospital of Ioannina, Ioannina, 451 10, Greece. Electronic address: ehatzim@cc.uoi.gr.
authors.forename: Eleftheria
authors.initials: E
authors.lastname: Hatzimichael
authors.affiliation: Department of Pharmacology, Faculty of Medicine, School of Life Sciences, University of Ioannina, Ioannina, 451 10, Greece. Electronic address: ppappas@cc.uoi.gr.
authors.forename: Periklis
authors.initials: P
authors.lastname: Pappas
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000009:adverse effects; D059250:Administration, Metronomic; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects / Q000276:immunology; D020714:Maximum Tolerated Dose; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D009389:Neovascularization, Pathologic; D019139:Tumor Escape / Q000187:drug effects*
chemical_list: D000276:Adjuvants, Immunologic; D020533:Angiogenesis Inhibitors
keywords: Angiogenesis; Antitumor immunity; Endothelial cell; Immunosuppression; Metronomic chemotherapy