Transcription Factors as Targets for Cancer Therapy: AP-1 a Potential Therapeutic Target

Virna   D.   Leaner; Howard      Donninger; Michael   J.   Birrer

Abstract

The field of cancer therapy is rapidly moving forward with the development of numerous prospective new agents designed to inhibit cellular factors involved in signal transduction, cell proliferation, and the onset of apoptosis. At the core of these biological processes are transcription factors that are the functional mediators of these effects. Transcription factors are the downstream targets of numerous signal transduction pathways that are central to the process of carcinogenesis. The Activator Protein-1 (AP-1) complex is one such factor that has a central role in multiple processes involved in tumorigenesis including proliferation, migration, invasion and metastasis. The focus of this review is, using AP- 1 as a model, to discuss transcription factors as targets for cancer therapy. The feasibility of targeted disruption of AP-1 by various agents such as dominant-negative mutants, small molecule inhibitors, transcription factor decoys (TFD), chemotherapeutic drugs, chemoprevention agents, siRNA and natural products will be explored.

Keywords: Cancer therapy, transcription factors, AP-1, dominant-negative mutants, TF-decoys, RNAi, small molecule inhibitors