Strategies for identifying molecular targets for cancer chemoprevention

Carcinogenesis is a multistage process involving hundreds of genes and gene products that regulate various cellular functions. The prevailing opinion today is that cancer might be prevented with small molecules that target specific or multiple cancer genes, signaling proteins and transcription factors. Some promising small molecule inhibitors include various dietary factors. Many of these factors appear to act on multiple tumor-associated cellular pathways with potent anticancer activity, low toxicity and limited adverse side effects. Combining agents or using individual agents that target multiple pathways is a strategy that is gaining acceptance. Powerful modern technologies are needed to accelerate the process of drug discovery especially to find compounds that can suppress multiple cellular signaling pathways. Combining supercomputer technologies, such as in silico screening, with protein structure determination and experimental laboratory validation assays to identify multiple protein targets of anticancer compounds is an example of technologies needed. This paper highlights two of the signaling pathways known to play an important role in carcinogenesis and describes the computational strategies used to identify small molecule inhibitors of these pathways. Finally, examples of molecules and their protein targets, which have been identified and validated by these combinational strategies for chemoprevention, are presented.