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Tumor necrosis factors (TNF) are small proteins that signal cells in the body, controlling cell death and inflammation. Dysregulation of TNF can lead to diseases, including cancer. TNF binds to and activates the TNF-R receptor, inducing cellular responses. TNF has been linked to Crohn’s disease and cancer. TNF inhibitors reduce inflammation in Crohn’s patients. TNF induces cell death of potentially cancerous cells, but also promotes inflammation. Scientists have developed forms of TNF that induce cancer cell death with little inflammation, leading to personalized treatment for cancer patients.
Tumor necrosis factors (TNF) are a family of small proteins used to signal cells throughout the body. The family consists of two proteins, named TNF-α and TNF-β. TNF-α is the more studied of the two proteins and is commonly referred to simply as “tumor necrosis factor”. Proteins are involved in controlling cell death and inflammation in the body. Dysregulation of TNF can lead to a number of diseases, including cancer.
Tumor necrosis factor proteins are classified as cytokines, a large class of proteins responsible for signaling to cells. TNF works by binding to and activating the tumor necrosis factor receptor (TNF-R) found on the surface of cells. Activation of TNF-R then induces a biological signal within the cell to produce a range of cellular responses. Specifically, when TNF binds to TNF-R, it signals increased inflammation in the surrounding area and can also instruct the cell to undergo programmed cell death. The amount of TNF within the body is tightly regulated in order to monitor the amount of cell death and inflammation occurring at any given time.
The binding of tumor necrosis factors to their receptors can become deregulated in the body, leading to a variety of diseases. In particular, TNF has been linked to Crohn’s disease, a disorder in which the colon is constantly inflamed. Crohn’s patients have more active TNF signaling to colon cells, which triggers sustained inflammation within the colon and causes Crohn’s disease. Many Crohn’s patients are prescribed drugs, called tumor necrosis factor inhibitors, which reduce the levels of active TNF in the colon and thus reduce inflammation to reduce the symptoms of the disease.
Tumor necrosis factor has also been implicated in several forms of cancer, such as breast and stomach cancer, which occur when cells that are supposed to undergo cell death fail to do so. In this sense, TNF fights cancer because it triggers cell death of potentially cancerous cells. On the other hand, inflammation is known to play a role in cancer progression, where sustained inflammation promotes the growth of tumors. Thus, although some features of TNF fight cancer by inducing cell death, other features of TNF signaling contribute to cancer by promoting inflammation.
Because of this dual role of TNF in cancer, the overall effects of tumor necrosis factor as a cancer treatment have been a matter of debate in cancer research. This has led to the development of a number of therapies designed to maintain the antitumor role of TNF, which decreases its inflammatory effect. To this end, scientists have developed forms of TNF that induce cancer cell death with little inflammation. Furthermore, the scientists found that treating tumors with TNF cocktails in combination with other therapies leads to cancer recession without inflammation. Ultimately, this research will enable physicians to deliver personalized tumor necrosis factor treatment to cancer patients to induce remission of tumors.
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