AACR special meeting in cancer research: Colon cancer-genetics to prevention

Novel functions and new approaches to the study of the multifaceted colorectal tumor suppressor gene, APC, were presented along with increasingly sophisticated mouse models of CRC. The application of technologies such as SAGE and oligonucleotide and cDNA microarray platforms to colon cancer research is at an exciting stage as these experimental approaches begin to bear fruit. These techniques have revolutionized the ability of cancer researchers to analyze the global changes in gene expression specific to each stage of multistep tumorigenesis and to correlate particular expression signatures with distinct histopathological phenotypes. As recently demonstrated for diffuse B-cell lymphomas (1), the capacity to molecularly profile histologically indistinguishable lesions may not only identify novel therapeutic targets and help predict disease progression and outcome, but perhaps more importantly, allow selection of the most appropriate treatment regimen. In addition, microarray analysis has the potential to provide insight into the fundamental mechanisms through which chemoprevention strategies exert their effects. New genes transcriptionally regulated during carcinogenesis and that may play a causal role in the growth and/or spread of colorectal tumor cells in vivo have already been identified using these methods. Many more await discovery as researchers optimize use of the new technologies in concert with improvements in gene clustering and statistical analysis software and apply them to new experimental systems. One area where global analysis of gene expression will be particularly useful is the study of the process of tumor invasion and metastasis, where our knowledge lags behind our understanding of the earlier events in CRC development. Secondly, expression profiling during experimental carcinogenesis in mice harboring defined genetic alterations on a defined genetic background should also be revealing. The ability to analyze many tumors from the same cancer-prone mouse will also result in fewer false positives.