Manohar Ratnam

..Regardless of the resistance mechanism, development and progression of the resistant tumors requires the persistence of a basal level of cycling cells during the treatment for which the underlying causes are unclear...

..Therefore, a potentially diverse set of ARE-independent mechanisms of AR interactions with target genes must underlie truly hormone depletion-insensitive gene regulation and proliferation in prostate cancer...

..We propose to further investigate this and other mechanisms of tamoxifen action and in the process, to identify lead compounds whose properties are superior to that of tamoxifen. ..

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..The studies should provide a solid foundation for designing clinical trials of new AML therapies and should also elucidate a fundamentally novel mechanism of gene regulation by retinoid receptors. ..

..They further promise to reveal novel mechanisms of tissue/tumor specific gene regulation with potential applications in the broad context of future gene therapy strategies. ..

..The mechanistic roles of such known and novel proteins in FR-mediated transport will be the subject of future investigations. The studies are expected to provide new insights of a fundamental nature into membrane transport processes. ..

..abstract_text> ..

..We propose to further investigate this and other mechanisms of tamoxifen action and in the process, to identify lead compounds whose properties are superior to that of tamoxifen. ..