Small Molecule Inhibitors of NF-κB and Their Therapeutic Potential in Leukaemia
The transcription factor nuclear factor kappa B (NF-κB) regulates the expression of over 200 genes. Many of these modulate cellular processes involved in the initiation, maintenance and growth of human malignancies. In this regard, both lymphoid and myeloid leukaemia often exhibit aberrant activation of NF-κB, implicating it in the pathology of these diseases and hence making it a promising therapeutic target. In addition, it is now appreciated that conventional cytotoxic agents can induce NF-κB activation, resulting in the suppression of tumour cell apoptosis and the development of drug resistance. Therefore, NF-κB inhibitors may prove clinically useful as single agents and in combination with chemotherapy. In this chapter we will review the current knowledge about the expression and regulation of NF-κB in different types of leukaemia and describe the promise, challenges and alternative strategies associated with the therapeutic targeting of NF-κB.