title: Chemotherapy resistance in ovarian cancer: new molecular perspectives.
abstract: OBJECTIVE
  To provide the obstetrician-gynecologist with the recent advances in mechanisms of chemotherapy resistance in ovarian cancer.
  
  
  METHODS
  A computerized search of articles published through September 1997 was performed on the MEDLINE Ovid and Cancerlit databases. Additional references were identified from the reference section of all selected papers.
  
  
  METHODS
  All identified references were evaluated as to their relevant contribution to our understanding of the basic mechanisms underlying the response to chemotherapy, the development of chemotherapy resistance in ovarian cancer, and possible strategies for therapy.
  
  
  RESULTS
  One hundred sixteen references were reviewed. A brief summary of the classic concepts on resistance to cisplatin and paclitaxel is provided, followed by a description of the basic mechanisms governing apoptosis and cell cycle arrest as well as their involvement in cell response to chemotherapy and the development of chemoresistance. Finally, a brief summary of the molecular alterations described in ovarian cancer, together with hypothetic strategies for gene-targeted therapy, are reported.
  
  
  CONCLUSIONS
  Cisplatin or paclitaxel chemotherapy induces arrest of the cell cycle or apoptosis in ovarian cancer cells. Tumor suppressor genes such as p53 play a paramount role in mediating this response and p21wAF1/CIP1 is a major mediator of p53-induced arrest of the cell cycle. Molecular alterations involving these tumor suppressor genes are related to the development of resistance to chemotherapy and represent possible targets for gene therapy in ovarian cancer.
authors.affiliation: Division of Gynecologic Oncology, University of Pennsylvania Medical Center, Philadelphia, USA.
authors.forename: G
authors.initials: G
authors.lastname: Coukos
authors.forename: S C
authors.initials: SC
authors.lastname: Rubin
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis; D002453:Cell Cycle; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D016158:Genes, p53 / Q000235:genetics; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics; D017239:Paclitaxel / Q000494:pharmacology / Q000627:therapeutic use; D014407:Tumor Cells, Cultured / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D017239:Paclitaxel; D002945:Cisplatin