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Tumor Progression and Therapeutic Resistance: An Overview

This volume contains highlights of a meeting that spanned the entire breadth of translational cancer research emanating from both academic laboratories and industry. It is the expectation of the editor that this effort will encourage further such interactions and accelerate progress in the field. Advances are occurring on multiple fronts, and the reports provided here include the discovery of molecular targets and pathways (oncogene, cell survival, tumor suppression, cell death), host–neoplasm interactions (cell adhesion, matrix proteases), early detection, and monitoring progression. The progress in our understanding of tumor progression and metastasis is presented, along with further information on immune surveillance, in vivo molecular imaging, animal models, and drug discovery and chemistry, high-throughput assays, mechanism determination, target validation, therapeutic window, and some progress in clinical trials for more advanced agents and targets. Patrick Everley and Bruce Zetter begin the volume with their report on the use of the techniques of proteomics and how this approach has been applied to the analysis of proteins in cancer, including the identification of temporal changes in protein levels as tumors develop and metastasize. For normal biological function to occur in cells, the temporal and spatial expression of proteins must be precisely regulated and coordinated. Shuttling between the nucleus and the cytoplasm by means of cellular signaling pathways mediated by protein kinases regulates the function of certain proteins. Shao-Chun Wang and MienChie Hung summarize findings that indicate a role for molecular localization in cancer. The incidence of melanoma is increasing rapidly: in just 40 years, the rate in the population has gone from 3 to 13 per 100,000. Activating mutations in BRAF have been identified in over 60% of melanomas, and Keiran Smalley and Meenhard Herlyn report on a therapeutic intervention involving the RAF inhibitor BAY 43-9006 and chemotherapy and the promise offered in research using small molecule inhibitors for targeting signaling cascades. Mark Nelson et al. address advances and setbacks in colorectal cancer, which is the third most fatal malignant neoplasm in the United States. The setbacks include the recall of cyclooxygenase-2 inhibitors from clinical trials, but these authors report on promising work using selenium compounds and further discuss the biochemical and molecular mechanisms for the anticancer effects of selenomethionine.