TNF-alpha and its inhibitors in cancer.
Tumor necrosis factor (TNF)-alpha is implicated in the same time in apoptosis and in cell proliferation. TNF-alpha not only acts as pro-inflammatory cytokine conducing to wide spectrum of human diseases including inflammatory diseases, but can also induce tumor development. The molecular mechanisms of TNF-alpha functions have been intensively investigated. In this review we covered TNF-alpha, the molecule, its signaling pathway, and its therapeutic functions. We provide a particular insight in its paradoxical role in tumor promotion and in its use as anti-tumor agent. This review considers also the recent findings regarding TNF-alpha inhibitors, their pharmacokinetics, and their pharmacodynamics. Six TNF-alpha inhibitors have been considered here: Infliximab, Adalimumab, Golimumab, CDP870, CDP571, Etanercept, and Thalidomide. We discussed the clinical relevance of their functions in treatment of several diseases such as advanced inflammatory rheumatic and bowel disease, with a focus in cancer treatment. Targeting TNF-alpha by these drugs has many side effects like malignancies development, and the long-term sequels are not very well explored. Their efficacy and their safety were discussed, underscoring the necessity of close patients monitoring and of their caution use.
Zidi
Inès
I
Laboratory of Biochemistry, Research Unit 02/UR/09-01, High Institute of Biotechnology, Institut Supérieur de Biotechnologie, BP 74, Avenue Tahar Haddad, Monastir 5000, Tunisia. ines.zidi@techemail.com
Mestiri
Souhir
S
Bartegi
Aghleb
A
Amor
Nidhal Ben
NB
D000818:Animals; D000970:Antineoplastic Agents / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D002986:Clinical Trials as Topic / Q000379:methods; D016503:Drug Delivery Systems; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000502:physiology*
D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha