Tumor necrosis factor (TNF) biology and cell death.
Tumor necrosis factor (TNF) was the first cytokine to be used in humans for cancer therapy. However, its role in the treatment of cancer patients is debated. Most uncertainties in this field stem from the knowledge that the pathways directly activated or indirectly affected upon TNF engagement with its receptors can ultimately lead to very different outcomes in terms of cell survival. In this article, we summarize the fundamental molecular biology aspects of this cytokine. Such a basis is a prerequisite to critically approach the sometimes conflicting preclinical and clinical findings regarding the relationship between TNF, tumor biology and anticancer therapy. Although the last decade has witnessed remarkable advances in this field, we still do not know in detail how cells choose between life and death after TNF stimulation. Understanding this mechanism will not only shed new light on the physiological significance of TNF-driven programmed cell death but also help investigators maximize the anticancer potential of this cytokine.
Bertazza
Loris
L
Department of Oncological and Surgical Sciences, University of Padova, via Giustiniani 2, 35128 Padova, Italy.
Mocellin
Simone
S
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D016923:Cell Death; D002470:Cell Survival; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry; D008954:Models, Biological; D008967:Molecular Biology; D011485:Protein Binding; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D016207:Cytokines; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha