Concepts, Mechanisms, and New Targets for Chemotherapy (Cancer Treatment and Research, 78)

__Concepts, Mechanisms, and New Targets for Chemotherapy__ describes new interconnections between rationally designed and empirically discovered compounds. One route that has not been travelled previously is that of protein kinase C inhibition. This pathway may be exploited to give potent inhibitors, such as the bryostatins, now in clinical trial. A summary is given of the current status of topoisomerase, focusing on recent clinical advances with camptothecin analogs based on connecting empiricism with concepts of drug selectivity. Modification of existing therapies based on the pursuit of leads arising from mechanistic studies is also being applied clinically on a wide scale. Greater understanding should follow from the studies of reversal of the multidrug resistant phenotype, on the use of hydroxyurea to reverse resistance mediated by extrachromosomal DNA, and on various aspects of the fluoropyrimidine pathways. Successful applications of chemotherapy to the treatment of specific diseases include the growing applications of systemic therapy using various skin malignancies. In prostate cancer, estramustine phosphate will likely play an expanding role. Taxanes are restructuring treatment regimens in breast cancer, and high-dose strategies are described with peripheral blood progenitor autografting in the treatment of ovarian and breast cancers. Front Matter....Pages i-x Front Matter....Pages 1-1 Potential for protein kinase C inhibitors in cancer therapy....Pages 3-27 Recent clinical advances with camptothecin analogues....Pages 29-43 The reversal of multidrug resistance....Pages 45-70 Fluoropyrimidine catabolism....Pages 71-93 Use of hydroxyurea to alter drug resistance of human tumor cells....Pages 95-114 Aspects of one-carbon folate cycling related to fluoropyrimidine and antifolate therapy....Pages 115-134 Front Matter....Pages 135-135 Systemic therapy of skin carcinoma....Pages 137-162 Estramustine revisited....Pages 163-184 Taxoid compounds in breast cancer: current status and future prospects....Pages 185-207 High-dose chemotherapy with peripheral blood progenitor autografting....Pages 209-226 Back Matter....Pages 227-237