Annals of the New York Academy of Sciences
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Ann. N. Y. Acad. Sci. · Oct 2007
ReviewDrugging the cancer chaperone HSP90: combinatorial therapeutic exploitation of oncogene addiction and tumor stress.
The molecular chaperone HSP90 has emerged as an exciting target for cancer treatment. We review the potential advantages of HSP90 inhibitors, particularly the simultaneous combinatorial depletion of multiple oncogenic "client" proteins, leading to blockade of many cancer-causing pathways and the antagonism of all of the hallmark pathological traits of malignancy. Cancer selectivity is achieved by exploiting cancer "dependencies," including oncogene addiction and the stressed state of malignant cells. ⋯ Potential new approaches are discussed, for example, interference with cochaperone binding and function in the superchaperone complex. Biomarkers for use with HSP90 inhibitors are described. We stress how basic and translational research has been mutually beneficial and indicate future directions to enhance our understanding of molecular chaperones and their exploitation in cancer and other diseases.
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Ann. N. Y. Acad. Sci. · Oct 2007
ReviewEvidence-based practice: limitations and successful implementation.
Evidence-based practice (EBP) has been heralded as the most appropriate way of ensuring that patients receive the most effective care possible. It does, however, have several limitations. It is also not enough just to locate and evaluate the evidence without implementing it. This paper discusses EBP and its limitations and potential barriers; it also suggests strategies for changing current practices to more evidence-based ones according to an accurate understanding of the concept of EBP.