Signal transducer and activator of transcription 3 as a therapeutic target for cancer and the tumor microenvironment

Arch Pharm Res. 2016 Aug;39(8):1085-99. doi: 10.1007/s12272-016-0795-8. Epub 2016 Aug 11.

Abstract

Signal transducer and activator of transcription 3 (STAT3) is a cytoplasmic transcription factor that modulates the transcription of a variety of genes to regulate important biological functions, including cell proliferation, differentiation, survival, angiogenesis, and immune response. Constitutive activation of STAT3 is important in oncogenic signaling and occurs at high frequency in human cancers, including diverse solid tumors and hematologic malignancies. Moreover, it is associated with a poor prognosis. The tumor microenvironment has recently been recognized as a key condition for cancer progression, invasion, angiogenesis, metastasis, and drug resistance by activation of STAT3 signaling. Therefore, understanding the biology associated with STAT3-mediated signaling cascades in the tumor microenvironment may offer the therapeutic potential to treat human cancers. This review presents an overview of the critical roles of STAT3 in the tumor microenvironment related to cancer biology and discusses recent advancements in the development of anticancer drugs that therapeutically inhibit STAT3 signaling cascades.

Keywords: Cancer; Inflammation; Signal transducer and activator of transcription 3 (STAT3); Tumor microenvironment.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / metabolism
  • Drug Delivery Systems / methods*
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • STAT3 Transcription Factor / antagonists & inhibitors*
  • STAT3 Transcription Factor / metabolism
  • Tumor Microenvironment / drug effects*
  • Tumor Microenvironment / physiology

Substances

  • Antineoplastic Agents
  • STAT3 Transcription Factor
  • STAT3 protein, human