Research over the past several decades has remarkably increased our knowledge of the molecular basis of human and experimental cancers. The effects of environmental carcinogens and biological agents on the activation of cellular oncogenes and inactivation of tumor suppressor genes have been documented in hundreds of different tumor types and model systems. Genes regulating cytokine and growth factor responses, intercellular adhesion, intracellular signaling, cell-cycle control, and DNA repair can all play a role in the development of cancer. Cumulative, and sometimes patterned, genetic damage seems to play a role in the malignant progression of tumors of various tissue types and the outcome of the cancer. With this seemingly endless supply of genetic targets for the generation of cancer, one must wonder how most people persist in a cancer-free state for extended periods of their life, and why certain cancers respond more favorably to therapy than others. Immune surveillance and specific immune responses to tumors may play a role in these reactions. Unfortunately the immune system itself can be a target for the development of a broad range of leukemias and lymphomas. Much has been learned about the growth regulation of normal T and B cells from a detailed analysis of those genetic changes that lead to the generation of leukemias. The use of genetic crosses to create bi-transgenic strains to evaluate interactions of specific oncogenes is a powerful type of analysis. Clearly, such models will be important in further defining the mechanisms operating in the genesis of cancer, and eventually in the testing of new modalities of cancer therapy. The surveillance of emerging cancers and their eradication may depend on the broadly reactive properties of cells called natural killers. This subpopulation of white cells can be subdivided by surface markers and functional properties. Many research articles discuss the evidence to support a special role for the NK population as the major antitumor population. This group of cells shows a dramatic response to IL-2, which includes changes in adhesive properties. Understanding the details of tumor-specific lymphocyte responses critically depends on the identification of tumor-specific antigens in naturally occurring cancers. The high dose cytoablative treatments used in many cancers require the replacement of essential hematopoietic cells and factors. Although many alternative approaches are used to kill cancer cells, they may all, in part activate a programed cellular mechanism of apoptosis. In this very fast moving field, many investigators proposed that the basic mechanisms of programmed cell death can be divided into three phases of induction, transduction and execution. The wide variety of inciting events may funnel down to a limited set of final commands common to many cell types. Understanding these pathways should have a major impact on the efficiency of all types of cancer therapy, including cellular-based mechanisms. |
