Elsevier

Obstetrics & Gynecology

Volume 92, Issue 2, August 1998, Pages 312-319
Obstetrics & Gynecology

Original Articles
Drug resistance in ovarian cancer: from the laboratory to the clinic

https://doi.org/10.1016/S0029-7844(98)00184-7Get rights and content

Abstract

Objective: To provide a review of the basic mechanisms of drug resistance in ovarian cancer and novel strategies to modulate drug resistance for the general obstetrician-gynecologist.

Data Sources: Relevant articles published through December 1996 were identified using the MEDLINE data base. Additional sources were found by cross-referencing.

Methods of Study Selection: Publications identified by the search were reviewed and evaluated critically for their relevance to drug resistance in ovarian cancer.

Tabulation, Integration, and Results: Each reference was reviewed for its contribution to the knowledge regarding mechanisms of chemotherapy resistance in ovarian cancer or strategies to modulate resistance.

Conclusion: Ovarian cancer patients have high response rates to initial chemotherapy after cytoreductive surgery. However, most will develop resistance to chemotherapy during the course of their treatment. There are multiple mechanisms resulting in drug resistance. Strategies to modulate drug resistance include dose intensity, various pharmacologic agents, and gene therapy.

Section snippets

Mechanisms of resistance

Drug resistance in ovarian cancer is broad and encompasses diverse, unrelated drugs, suggesting more than one mechanism of resistance. Drug resistance can be classified as either intrinsic or acquired. Table 1 lists mechanisms resulting in either intrinsic or acquired drug resistance. Some of these can overlap. Figure 1 diagrams the interaction of these mechanisms at the cellular level.

Intrinsic resistance represents resistance at the time of initial treatment and is an inherent property of

Modulation of chemoresistance

Efforts to improve the efficacy of chemotherapy and circumvent chemoresistance have included dose intensification of active agents. In 1987, Levin et al17 reported an association between outcome and dose intensity for platinum-based agents alone or in multiagent regimens. Their analysis suggested a significant correlation between increased-dose intensity and improved response and survival rates for patients treated with cisplatin-based combinations. However, the correlation was found only up to

Summary

It is evident from most studies that resistance is probably caused by interaction of multiple factors and a single biochemical modulator is not likely to be completely successful in reversing drug resistance. Currently, our knowledge of resistance mechanisms is incomplete and must be expanded. Although some of the resistance mechanisms reviewed here have been evaluated in nonovarian cancer neoplasms, they provide useful models to study in ovarian cancer.

Unfortunately, most regimens discussed

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