title: Modulating the tumor microenvironment with RNA interference as a cancer treatment strategy.
abstract: The tumor microenvironment is composed of accessory cells and immune cells in addition to extracellular matrix (ECM) components. The stromal compartment interacts with cancer cells in a complex crosstalk to support tumor development. Growth factors and cytokines produced by stromal cells support the growth of tumor cells and promote interaction with the vasculature to enhance tumor progression and invasion. The activation of autocrine and paracrine oncogenic signaling pathways by growth factors, cytokines, and proteases derived from both tumor cells and the stromal compartment is thought to play a major role in assisting tumor cells during metastasis. Consequently, targeting tumor-stroma interactions by RNA interference (RNAi)-based approaches is a promising strategy in the search for novel treatment modalities in human cancer. Recent advances in packaging technology including the use of polymers, peptides, liposomes, and nanoparticles to deliver small interfering RNAs (siRNAs) into target cells may overcome limitations associated with potential RNAi-based therapeutics. Newly developed nonviral gene delivery approaches have shown improved anticancer efficacy suggesting that RNAi-based therapeutics provide novel opportunities to elicit significant gene silencing and induce regression of tumor growth. This chapter summarizes our current understanding of the tumor microenvironment and highlights some potential targets for therapeutic intervention with RNAi-based cancer therapeutics.
authors.affiliation: Laboratory for Cardiovascular Research, Center for Anatomy and Cell Biology, Medical University of Vienna, Vienna, Austria.
authors.forename: Karin
authors.initials: K
authors.lastname: Zins
authors.forename: Mouldy
authors.initials: M
authors.lastname: Sioud
authors.forename: Seyedhossein
authors.initials: S
authors.lastname: Aharinejad
authors.forename: Trevor
authors.initials: T
authors.lastname: Lucas
authors.forename: Dietmar
authors.initials: D
authors.lastname: Abraham
mesh_terms: D000818:Animals; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D005109:Extracellular Matrix / Q000737:chemistry / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D006801:Humans; D061986:MCF-7 Cells; D016173:Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D015674:Mammary Neoplasms, Animal / Q000098:blood supply / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D051379:Mice; D009389:Neovascularization, Pathologic; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics* / Q000378:metabolism; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism* / Q000473:pathology; D059016:Tumor Microenvironment; D023041:Xenograft Model Antitumor Assays
chemical_list: D034741:RNA, Small Interfering; D016173:Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor