Importance of TNF-alpha and its alterations in the development of cancers

•TNF-alphaα plays a role in pathogenesis of many diseases, including malignancies.•This makes TNF-α a promising therapeutic target.•TNF-α also participates in apoptosis and necrosis, angiogenesis and cellular migration.•TNF-α exerts cancerogenesis via its receptors and other cytokines in its signaling pathways.•Therapeutic levels of TNF-α have neoplastic effects.•TNF-α plays anti-neoplastic roles by disruption of tumor vasculature and induction of necrosis.•TNF-α is a double-edged sword due to its paradoxical effects encountering with neoplasms.•Anti-neoplastic therapies based on TNF-α must address its miscellaneous signaling pathways. TNF-alpha is involved in many physiologic and pathologic cellular pathways, including cellular proliferation, differentiation, and death, regulation of immunologic reactions to different cells and molecules, local and vascular invasion of neoplasms, and destruction of tumor vasculature. It is obvious that because of integrated functions of TNF-alpha inside different physiologic systems, it cannot be used as a single-agent therapy for neoplasms; however, long-term investigation of its different cellular pathways has led to recognition of a variety of subsequent molecules with more specific interactions, and therefore, might be suitable as prognostic and therapeutic factors for neoplasms. Here, we will review different aspects of the TNF-alpha as a cytokine involved in both physiologic functions of cells and pathologic abnormalities, most importantly, cancers.