The Dual Role of Tumor Necrosis Factor (TNF) in Cancer Biology
Abstract:Tumor necrosis factor (TNF) is a cytokine with well known anticancer properties and is being utilized as anticancer agent for the treatment of patients with locally advanced solid tumors. However, TNF role in cancer biology is debated. In fact, in spite of the wealth of evidence supporting its antitumor activity, the cascade of molecular events underlying TNF-mediated tumor regression observed in vivo is still incompletely elucidated. Furthermore, some preclinical findings suggest that TNF may even promote cancer development and progression.
With this work we intend to summarize the molecular biology of TNF (with particular regard to its tumor-related activities) and review the experimental and clinical evidence currently available describing the complex and sometime apparently conflicting relationship between this cytokine, cancer biology and antitumor therapy. We also propose a model to explain the dual effect of TNF based on the exposure time and cytokine levels reached within the tumor microenvironment. Finally, we overview recent research findings that might lead to new ways for exploiting the anticancer potential of TNF in the clinical setting.
Keywords: (DISC); (SODD); ANTI-TNF THERAPY; ANTICANCER; Cancer anorexia-cachexia syndrome; Coley's toxin; FLICE; NFkB; NFkB Pathway; NOS; NSAID; PKB/Akt; TACE; TNF; TNF Muteins; TNF PATHWAY; TNF-antagonists; TNF-converting enzyme; Tumor necrosis factor; angiogenesis; antineoplastic agents; apoptosis; biology; cancer; cancer biotherapy; carcinogenesis; cathepsin-B; ceramide; chemotherapeutic agents; haemorrhagic necrosis; isolated hepatic perfusion; isolated limb perfusion; malignant cells; murine fibrosarcoma; pro-coagulant tissue factor; proapoptotic factors; programmedcell-death; protein kinase-C; single nucleotide polymorphisms; therapy; thromosis; transcription factors
Document Type: Research Article
Publication date: October 1, 2010
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