Signal transcluction pathways in cancer development and as targets for cancer prevention

Carcinogenesis is a multifaceted and complex process that profoundly affects numerous genes and gene products important in the regulation of various cellular functions. A major focus of much of the work from this laboratory has been the elucidation of crucial molecular and cellular mechanisms in cancer development and prevention. Our goal continues to be the clarification of signal transduction pathways induced by carcinogens and tumor promoters as causative factors for cancer development. In order to facilitate the development of chemopreventive and chemotherapeutic agents that specifically target molecules important in cancer development, we must know the enemy-we must understand carcinogenesis. The prevailing thought today is that cancer may be prevented or treated by targeting specific cancer genes, signaling proteins, and transcription factors. Cancer is a multistage process, consisting of initiation, promotion, and progression stages. Although each stage may be a possible target for chemopreventive agents, the promotion stage has the most potential to be reversed because of its extensive length. By focusing on the molecular mechanisms explaining how normal cells can undergo neoplastic transformation induced by tumor promoters, we have discovered that several specific transcription factors and proteins, such as activator protein-1 (AP-1) and c-Jun N-terminal kinases (JNKs), are critical in cancer development and are significant targets for cancer prevention and treatment. We are a leader in the elucidation of the mechanisms explaining the paradoxical role of arsenic in cancer development and the role of ultraviolet (UV) irradiation in the development of skin cancer. Another major goal is to identify anticancer agents that have low toxicity with fewer adverse side effects, which may be used alone or in combination with traditional chemotherapeutic agents to prevent or treat cancer. Many dietary factors have potent anticancer activities that work through, as yet, unknown mechanisms. Over the years, we have been working to identify those mechanisms through our work with signal transduction pathways. Various dietary factors, including many isolated from green and black tea, potatoes, broccoli, peanuts, ginger root, and rice, mediate crucial cellular communication pathways in cancer development and prevention. This review summarizes work in signal transduction pathways involved in neoplastic cell transformation and carcinogenesis and presents strong evidence for these pathways as effective targets for chemopreventive agents. © 2005 Elsevier Inc. All rights reserved.