Modulation of neoplastic development: concepts and examples

Chemical carcinogenesis is classically considered as a multiphasic process within which one identifies an initiation phase followed by a phase of promotion and finally progression and/or conversion. The concept of modulation of neoplastic development will be proposed. That concept characterizes any treatment able to modify the evolution of a carcinogenic process. Such a modification is either an acceleration or a slowing down of carcinogenesis. It is not fully equivalent to promotion since it is not an obligatory phase of carcinogenesis. After an initiating treatment, the evolution of carcinogenesis can thus be modulated either positively or negatively. Modulating agents of liver carcinogenesis can be chemical carcinogens, non-genotoxic xenobiotics, endogenous factors, food ingredients, surgery, infectious agents. Their effect on the development of preneoplastic lesions can be both quantitatively and qualitatively different from their effect on the appearance of liver cancers. They could act through cellular or systemic metabolic perturbations linked with cell proliferation.