Abstract
Ovarian cancer of epithelial origin remains one of the most lethal malignancies despite response rates of more than 80% in first-line combination chemotherapy with platinum drugs and taxanes following surgery. Poor overall prognosis is mainly due to acquired resistance of the recurring tumor mass to initially used and other chemotherapeutic agents. Therefore, novel therapeutic approaches are based on concepts to prevent (improvement of tumor exposure to drugs) or circumvent drug resistance, e.g. with new drugs structurally related to the currently used cytotoxic agents, other types of cytotoxic substances, or with targetspecific novel drugs interfering with signaling and apoptotic pathways. In addition, acquired molecular characteristics of drug resistant ovarian carcinoma cells can be defined by expression profiling at different stages of therapy and might be used as specific targets for tumor-suppressing drugs and prodrugs containing cytotoxic components. Revelation of mechanistic details of drug resistance also provides the basis for the development of therapies with novel or conventional antitumor drugs in combination with specific inhibitors able to re-establish chemosensitivity. In this review, we summarize novel approaches in the treatment of ovarian cancer progressed to drug resistant stages and focus on the discussion of recently reported experimental and early clinical results with potentially useful strategies to overcome or modulate acquired drug resistance.
Keywords: Ovarian cancer, drug resistance, GST, signaling, apoptosis, chemotherapy, novel agents
Current Cancer Drug Targets
Title: Molecular Targets of Ovarian Carcinomas with Acquired Resistance to Platinum/Taxane Chemotherapy
Volume: 6 Issue: 3
Author(s): Christian Kurzeder, Georg Sauer and Helmut Deissler
Affiliation:
Keywords: Ovarian cancer, drug resistance, GST, signaling, apoptosis, chemotherapy, novel agents
Abstract: Ovarian cancer of epithelial origin remains one of the most lethal malignancies despite response rates of more than 80% in first-line combination chemotherapy with platinum drugs and taxanes following surgery. Poor overall prognosis is mainly due to acquired resistance of the recurring tumor mass to initially used and other chemotherapeutic agents. Therefore, novel therapeutic approaches are based on concepts to prevent (improvement of tumor exposure to drugs) or circumvent drug resistance, e.g. with new drugs structurally related to the currently used cytotoxic agents, other types of cytotoxic substances, or with targetspecific novel drugs interfering with signaling and apoptotic pathways. In addition, acquired molecular characteristics of drug resistant ovarian carcinoma cells can be defined by expression profiling at different stages of therapy and might be used as specific targets for tumor-suppressing drugs and prodrugs containing cytotoxic components. Revelation of mechanistic details of drug resistance also provides the basis for the development of therapies with novel or conventional antitumor drugs in combination with specific inhibitors able to re-establish chemosensitivity. In this review, we summarize novel approaches in the treatment of ovarian cancer progressed to drug resistant stages and focus on the discussion of recently reported experimental and early clinical results with potentially useful strategies to overcome or modulate acquired drug resistance.
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Kurzeder Christian, Sauer Georg and Deissler Helmut, Molecular Targets of Ovarian Carcinomas with Acquired Resistance to Platinum/Taxane Chemotherapy, Current Cancer Drug Targets 2006; 6 (3) . https://dx.doi.org/10.2174/156800906776842975
DOI https://dx.doi.org/10.2174/156800906776842975 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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