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

ABSTRACT

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.

KEYWORDS:

• Cancer
• clinical trial
• drug resistance
• immune response
• signal transducer and activator of transcription 3
• STAT3

Article highlights

• STAT3 is implicated in both innate and adaptive immunity

• STAT3 mutations such as its hyperactivation or inactivation are associated with cancer

• STAT3 inhibitors are emerging as a promising approach in solid tumors

• Combining immunotherapy and STAT3 inhibitors should be evaluated in further studies

• The cytotoxicity of STAT3 inhibitors is related to its key role in a variety of physiological processes

• The contribution of STAT3 to acquired drug resistance merits careful consideration

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.