Camptothecins in Cancer Therapy
Val R. Adams
Springer Science & Business Media, Oct 27, 2007 - Medical - 460 pages
A critical review our current understanding of camptothecins, their shortcomings, and of the possibilities for improving their clinical performance. The authors discuss new camptothecin analog development, drug delivery issues for optimizing their anticancer activity, and their potential use in a variety of different cancers. Additional chapters describe what is known about the biochemistry, the pharmacology, and the chemistry of the camptothecins, including the mechanism of topoisomerase and how camptothecins poison this enzyme, the use of animal models in defining the anticancer potential of camptothecins, and the question of camptothecin resistance.
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administered agents anticancer antitumor activity binding Biol Chem camptothecin analog Cancer Chemother Pharmacol carboplatin carcinoma cell lines cell lung cancer cellular chemotherapy cisplatin cleavage complexes Clin Cancer Res clinical trials colorectal cancer combination covalent CPT analogs cycles cytarabine cytotoxicity diarrhea DNA damage DNA topoisomerase dose drug E-ring enzyme etoposide evaluated exatecan gemcitabine gene grade homocamptothecin inhibition irinotecan irinotecan CPT-11 lactone leukemia liposomal Liu LF lung cancer lurtotecan malignant median survival metabolite metastatic mice mutant myelosuppression neutropenia NSCLC oral ovarian cancer paclitaxel partial response patients with advanced pharmacokinetic pharmacologic phase II study phase II trial plasma Pommier preclinical Proc Am Soc protein refractory regimen relapsed replication resistance response rate rubitecan schedule SCLC small cell lung Soc Clin Oncol solid tumors stability study of topotecan therapy thrombocytopenia TOP-I Top1 cleavage Top1 poisons topoisomerase I inhibitor topotecan toxicity treatment tumor untreated vitro weeks xenografts yeast
Page v - I do not feel obliged to believe that the same God who has endowed us with sense, reason, and intellect has intended us to forgo their use.