Molecular targets of ovarian carcinomas with acquired resistance to platinum/taxane chemotherapy.
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 target-specific 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.
Kurzeder
Christian
C
University of Ulm Medical School, Department of Obstetrics and Gynaecology, Germany.
Sauer
Georg
G
Deissler
Helmut
H
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001952:Bridged-Ring Compounds / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D009944:Organoplatinum Compounds / Q000627:therapeutic use*; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D015398:Signal Transduction / Q000187:drug effects; D043823:Taxoids / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D001952:Bridged-Ring Compounds; D009944:Organoplatinum Compounds; D043823:Taxoids; C080625:taxane