c-Myc and Downstream Targets in the Pathogenesis and Treatment of Cancer
Pp. 340-379 (40)
Sam Robson, Inga Pukonen, Sylvie Abouna, Stella Pelengaris and Michael Khan
The c-Myc oncoprotein is a master regulator of genes involved in diverse cellular processes. Situated upstream of signalling pathways regulating cellular replication/growth as well as apoptosis/growth arrest, c-Myc may help integrate processes determining cell numbers and tissue size in physiology and disease. In cancer, this ‘dual potential’ allows cMyc to act as its own tumour suppressor. Evidently, given that deregulated expression of c-myc is present in most, if not all, human cancers (Table 1) and is associated with a poor prognosis, by implication these in-built ‘failsafe’ mechanisms have been overcome.
To explore the complex activity of c-Myc and its potential as a therapeutic target ‘post-genome era’ technologies for determining global gene expression alongside advanced new models for the study of tumourigenesis in vivo have proved invaluable. Thus, many recent studies have provided encouragement for the therapeutic targeting of c-Myc in cancer and have revealed new protein targets for manipulating aspects of c-Myc activity. The remarkable regression of even advanced and genetically unstable tumours, seen following deactivation of c-Myc in various models is particularly exciting.
This review will discuss what is known about the role of c-Myc in growth deregulation and cancer and will conclude with a discussion of the most promising recent developments in c-Myc-targeted therapeutics.
c-Myc, apoptosis, growth, cell-cycle, differentiation, cancer, diabetes, regression, gene expression
Biological Sciences, Biomedical Research Institute, University of Warwick, Coventry, CV4 7AL, UK.