Biology and Impact of Signal Transducers and Activators of Transcription and Their Regulators as Targets in Cancer Therapy

Edith      Pfitzner; Frank      Nonnenmacher; Daniela      Baus

Abstract

While chemo- and radiotherapy is far developed and successfully employed by default for cancer treatment, severe side effects point to the urgent need for more specific therapies based on the molecular mechanisms of this disease. Strategies to specifically inhibit signaling pathways that are known to force proliferation, prevent apoptosis or promote angiogenesis are expected to have a substantial impact on the future direction taken in cancer therapy. The Janus Kinase (JAK) / Signal transducer and activator of transcription (STAT) pathway is one major signaling pathway converting the signal of cytokines, growth factors and hormones into gene expression programs regulating essential cellular functions like proliferation, differentiation and survival. The suppressors of cytokine signaling (SOCS) as well as phosphatases normally tightly regulate the JAK/STAT pathway. Frequently, however this pathway is constitutively activated in a wide variety of human malignancies and substantially contributes to carcinogenesis. Consequently, new strategies for targeting the JAK/STAT pathway have been developed. This review discusses the biology of the JAK/STAT signaling pathway, which offers several molecular strategies for therapeutic interruption.

Keywords: STAT, JAK, cancer, cytokine, SOCS, signaling, inhibitors