Cancer chemopreventive agents-drugs for the 21st century?

After a quarter of a century of rapid advances in cancer research, the focus of oncological drug development has shifted from cytotoxic chemotherapy to rationally designed agents that target specific molecules associated with malignant cells or their environment. Carcinogenic process is driven by mutation, but there are many epigenetic variables which could be the targets of early intervention before invasion and metastasis occur. Chemoprevention is the inhibition, retardation or reversal of carcinogenic processes by pharmacological or natural agents targeting these pathways in high-risk individuals. This approach was developed more than 30 years ago and its credibility was enhanced by the positive results of clinical trials involving subjects with risk of developing breast cancer and colon tumors. So far however, not many clinical trials provided satisfying results, not only because of the lack of efficacy or side toxic effects of chemopreventive agents, but also the lack of precise biomarkers monitoring their effects. In spite of all these obstacles, the field of cancer chemoprevention is very active, not only because of its accelerating scientific base, but also because is vitally needed. New information from molecular studies has identified specific molecular targets for chemopreventive agents. These include regulatory molecules such as Nrf2, epidermal growth factor receptor kinases, components of the Janus kinase-signal transducers and activators of transcription (JAK-STAT) pathway, nuclear factor-kappaB, and cyclin D. The development of new drugs for the control of these targets that are both safe and effective will be important for the future of cancer chemoprevention.