title: Targeting breast cancer through its microenvironment: current status of preclinical and clinical research in finding relevant targets.
abstract: It is increasingly evident that not only breast cancer cells, but also the tissue embedding these cells: the tumor microenvironment, plays an important role in tumor progression, metastasis formation and treatment sensitivity. This review focuses on the current knowledge of processes by which the microenvironment affects breast cancer, including formation of the metastatic niche, metabolic stimulation, stimulation of tumor cell migration, immune modulation, angiogenesis and matrix remodeling. The number of drugs targeting key factors in these processes is expanding, and the available clinical data is increasing. Therefore current strategies for intervention and prediction of treatment response are outlined. At present, targeting the formation of the metastatic niche and metabolic stimulation by the breast cancer microenvironment, are already showing clinical efficacy. Intervening in the stimulation of tumor cell migration and immune modulation by the microenvironment upcoming fields of great research interest. In contrast, targeting microenvironmental angiogenesis or matrix remodeling appears to be of limited clinical relevance in breast cancer treatment so far. Further research is warranted to optimize intervention strategies and develop predictive tests for the relevance of targeting involved factors within the microenvironment in order to optimally personalize breast cancer treatment.
authors.affiliation: Department of Medical Oncology, University Medical Center Groningen, The Netherlands.
authors.forename: H H
authors.initials: HH
authors.lastname: Nienhuis
authors.affiliation: Department of Medical Oncology, University Medical Center Groningen, The Netherlands.
authors.forename: S B M
authors.initials: SB
authors.lastname: Gaykema
authors.affiliation: Department of Medical Oncology, University Medical Center Groningen, The Netherlands.
authors.forename: H
authors.initials: H
authors.lastname: Timmer-Bosscha
authors.affiliation: Department of Medical Oncology, University Medical Center Groningen, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Jalving
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, The Netherlands.
authors.forename: A H
authors.initials: AH
authors.lastname: Brouwers
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, The Netherlands; Department of Hospital and Clinical Pharmacy, University Medical Center Groningen, The Netherlands.
authors.forename: M N
authors.initials: MN
authors.lastname: Lub-de Hooge
authors.affiliation: Department of Pathology, University Medical Center Groningen, The Netherlands.
authors.forename: B
authors.initials: B
authors.lastname: van der Vegt
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
authors.forename: B
authors.initials: B
authors.lastname: Overmoyer
authors.affiliation: Department of Medical Oncology, University Medical Center Groningen, The Netherlands.
authors.forename: E G E
authors.initials: EG
authors.lastname: de Vries
authors.affiliation: Department of Medical Oncology, University Medical Center Groningen, The Netherlands. Electronic address: c.p.schroder@umcg.nl.
authors.forename: C P
authors.initials: CP
authors.lastname: Schröder
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000378:metabolism; D035843:Biomedical Research / Q000379:methods; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002986:Clinical Trials as Topic / Q000379:methods; D016503:Drug Delivery Systems / Q000379:methods / Q000639:trends*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D006801:Humans; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D059016:Tumor Microenvironment / Q000187:drug effects* / Q000502:physiology
chemical_list: D000970:Antineoplastic Agents
keywords: Biomarkers; Breast cancer; Metabolism; Metastasis; Microenvironment; Targeted therapy