An update on investigational therapies that target STAT3 for the treatment of cancer

Introduction: Signal transducer and activator of transcription 3 (STAT3) is involved in cancer initiation and resistance to chemo-radiation therapies and targeted agents. The role of STAT3 in inflammation and immunity together with its involvement in a variety of diseases including genitourinary, gastrointestinal, lung, ovarian and brain tumors makes STAT3 an ideal candidate for therapeutic strategies. Areas Covered: The authors provided an overview on STAT3 inhibitors and examined the most recent results obtained by these agents in cancer patients. The authors discussed the results published since 2015 and the ongoing clinical trials on anti-STAT3 agents in cancer patients. The authors also provide our opinion on the future perspectives of this therapeutic approach in this context. The manuscript includes information from trial databases and scientific literature. Expert Opinion: Future challenges include the development of non-peptide small-molecule inhibitors of STAT3 designed to directly inhibit STAT3 activity. In addition, inhibitors of STAT3/STAT3 nuclear translocation or DNA binding activity are also emerging as novel promising therapeutic approaches A better comprehension of the role of STAT3 in modulating immune response together with advances in understanding the mechanisms of STAT3-induced chemo and/or radio-resistance will also help the design of combined strategies in cancer patients.