Hans E. Huber, Kenneth S. Koblan and David C. Heimbrook* Pages 13 - 34 ( 22 )
The recent elucidation of many of the pathways involved in the regulation of cellular proliferation provides new opportunities for therapeutic intervention in the treatment of cancer. The inherent specificity of many of these protein-protein interactions should provide great selectivity, and emerging models of cell cycle control suggest that disrupting growth factor signalling pathways might selectively induce programmed cell death in cancer cells. However, many of these protein-protein interactions appear to occur over fairly large surfaces, suggesting that the identification of small molecules with the necessary affinity and specificity to disrupt these interactions in vivo represents a challenging undertaking. In the current review, we highlight three particular targets in the growth factor signalling pathways : growth factor - receptor binding, using Gastrin Releasing Peptide as a specific example; SH2 / SH3 domain interactions; and viral oncoprotein interaction with cellular proteins in the nucleus, focusing on the binding of Human Papillomavirus proteins with cellular growth suppressor gene products. These studies highlight both the promise and the pitfalls of selectively targeting protein-protein interactions for the treatment of cancer.