Inhibition of tumorigenesis in animals

Animal models are an important component of chemopreventive research. They provide a means of identifying effective compounds, of carrying out fundamental investigations into their mechanisms of action, of determining how they can be used optimally, of evaluating toxicity and, ultimately, of providing an information base for developing intervention trials in humans. They are available for evaluating the effects of chemopreventive agents on the occurrence of cancer in most major organ sites. For some cancers, improved models are required. One such is squamous cell carcinoma of the bronchi, a major cancer in humans. There are three major groups of animal models: the first group involves administration of chemical or physical carcinogens to produce carcinogenesis; the second group consists of mice in which viruses, usually endogenous, are the major causative agents; and the third group entails use of transgenic mice. Most chemopreventive agents investigated in animal models can be placed into three broad categories: compounds preventing attacking molecules from reaching or reacting with critical target sites (blocking agents); compounds decreasing sensitivity of target tissues to carcinogenic stimuli; and compounds preventing the evolution of the neoplastic process (suppressing agents). There is increasing interest in the use of agent combinations rather than single agents as a means of obtaining increased efficacy and minimizing toxicity. Combinations studied thus far entail the use of at least one suppressing agent, in combination with either a blocking agent or a second suppressing agent. The development of optimal strategies for human intervention trials can be facilitated by the use of animal models mimicking the neoplastic process in humans. It is important to exploit this potential to its maximum degree.