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Mechanisms and modulation of resistance to chemotherapy in ovarian cancer
Author(s) -
Perez Raymond P.,
Hamilton Thomas C.,
Ozols Robert F.,
Young Robert C.
Publication year - 1993
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.2820710424
Subject(s) - medicine , ovarian cancer , drug resistance , cisplatin , chemotherapy , drug , clinical trial , oncology , pharmacology , cancer , efficacy , drug development , bioinformatics , cancer research , biology , microbiology and biotechnology
Chemotherapy for advanced ovarian cancer remains sub‐optimal. Despite the improvements in objective response rates realized with cisplatin‐based combination chemotherapeutic regimens, most patients still die of refractory cancer. Drug resistance has emerged as the single most important determinant of treatment outcome. Laboratory studies have provided substantial insights into the cellular mechanisms of resistance to the commonly used chemotherapeutic agents. Decreased drug accumulation, metabolic drug inactivation, and repair or tolerance to drug‐induced cellular injury all contribute to resistance at the cellular level. Identification of these mechanisms has facilitated the development of specific treatment strategies, many of which are in or nearing clinical trials. These strategies include dose intensification, inhibition of P‐glycoprotein function, inhibition of cellular glutathione synthesis, and inhibition of cellular DNA repair. The initial results from clinical trials that use these strategies provide reasonable grounds for optimism. In addition, efforts to identify new drugs with activity against resistant cells continue. One such drug, taxol, has significant activity in tumors refractory to conventional therapy. These approaches offer hope that intensive laboratory and clinical efforts ultimately will translate into real improvements in the efficacy of chemotherapy for ovarian cancer.