Overview of the STAT-3 signaling pathway in cancer and the development of specific inhibitors (Review)

Abstract

Signal transducer and activator of transcription (STAT) proteins represent novel therapeutic targets for the treatment of cancer. In particular, STAT-3 serves critical roles in several cellular processes, including the cell cycle, cell proliferation, cellular apoptosis and tumorigenesis. Persistent activation of STAT-3 has been reported in a variety of cancer types, and a poor prognosis of cancer may be associated with the phosphorylation level of STAT-3. Furthermore, elevated STAT-3 activity has been demonstrated in a variety of mammalian cancers, both in vitro and in vivo. This indicates that STAT-3 serves an important role in the progression of numerous cancer types. A significant obstacle in developing STAT-3 inhibitors is the demonstration of the antitumor efficacy in in vivo systems and the lack of animal models for human tumors. Therefore, it is crucial to determine whether available STAT-3 inhibitors are suitable for clinical trials. Moreover, further preclinical studies are necessary to focus on the impact of STAT-3 inhibitors on tumor cells. When considering STAT-3 hyper-activation in human cancer, selective targeting to these proteins holds promise for significant advancement in cancer treatment. In the present study, advances in our knowledge of the structure of STAT-3 protein and its regulatory mechanisms are summarized. Moreover, the STAT-3 signaling pathway and its critical role in malignancy are discussed, in addition to the development of STAT-3 inhibitors in various cancer types.