Abstract:
:The current reference treatment of hormone-refractory prostate cancer consists mainly of chemotherapy with docetaxel. To improve the management of advanced prostate cancer, one should examine the benefits of adding other agents to docetaxel. We examined the growth inhibitory effects of a triple combination, including the anti-epidermal growth factor receptor drug erlotinib, docetaxel and 5-fluoro-5'-deoxyuridine (the main intermediary metabolite of capecitabine), on the human prostate cancer cell lines PC3 and DU145, which are both devoid of androgen receptors. Marked synergistic cytotoxic effects were observed with the application of the double combination of erlotinib-5-fluoro-5'-deoxyuridine for both cell lines and to a lesser magnitude with the triple combination. For PC3 cells, all conditions resulted in synergistic interactions. The combination between erlotinib and docetaxel resulted in an approximately 50% reduction in thymidylate synthase activity (the molecular target of 5-fluorodeoxyuridine monophosphate, the active capecitabine anabolite) with an higher impact observed with DU145 cells than with PC3 cells. Neither erlotinib nor docetaxel alone displayed marked effects on thymidine phosphorylase activity (the enzyme that governs at the cellular level the final and crucial step in the activation cascade of capecitabine), in contrast to their combination that resulted in a strong increase in thymidine phosphorylase activity in PC3 cells. These data may serve as a rational basis for setting up clinical trials in advanced prostate cancer combining epidermal growth factor receptor-targeting agents like erlotinib together with docetaxel and capecitabine.
journal_name
Anticancer Drugsjournal_title
Anti-cancer drugsauthors
Fischel JL,Ciccolini J,Formento P,Ferrero JM,Milano Gdoi
10.1097/01.cad.0000224444.23953.90subject
Has Abstractpub_date
2006-08-01 00:00:00pages
807-13issue
7eissn
0959-4973issn
1473-5741pii
00001813-200608000-00008journal_volume
17pub_type
杂志文章abstract::This study was performed to evaluate the role of protein kinase C (PKC) activity in the development of chemoresistance in clinical breast cancer cells. To simulate the clinical situation, native tumor cells derived from 10 patients with advanced breast cancer were brought into short-term cultures, and treated with ant...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
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journal_title:Anti-cancer drugs
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pub_type: 杂志文章,评审
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journal_title:Anti-cancer drugs
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journal_title:Anti-cancer drugs
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journal_title:Anti-cancer drugs
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journal_title:Anti-cancer drugs
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