An Overview of Tumor Necrosis Factor-α on Pathophysiological Mechanisms, Relevant Therapeutic Status in Breast Cancer

Abstract

TNFα is an essential pro-inflammatory cytokine that is prevalent in the tumor microenvironment and is involved in mediating or activating many significant signaling pathways which result in inflammation, apoptosis, and tumor cell proliferation, survival, and invasiveness. In breast cancer, TNFα is involved throughout all stages from occurrence, development, procession, and metastasis to recurrence. Researchers have pointed out that TNFα plays a major role in the estrogen biosynthesis pathway, especially in the process of adipose tissue switching to estrogen. In the breast tumor microenvironment, TNFα may participate in the mediation of estrone sulfatase expression and activity. In terms of therapeutics, methods to suppress TNFα signaling in breast cancer have been proposed. To neutralize the pro-tumor and inflammatory effects of TNFα, most research opts to use anti-TNFα antibodies. According to the research, the administration of TNFα antagonists can suppress the development of breast cancer cells and strengthen the chemotherapeutic response when used as adjuvant therapy with chemotherapy. Consequently, tumor drug resistance can be well controlled. However, some side effects like systemic toxicity, the typical skin lesion, and the increasing risk of developing new cancers are still major issues. More extensive clinical trials have to be carried out for deeper investigation. This paper gives an overview of the intrinsic features of TNFα as a cytokine and gets insight into the pathophysiological mechanisms mediated by TNFα in breast cancer. Furthermore, the current state of knowledge in terms of TNF-related therapeutic strategies was adequately summarized and discussed.