Original ArticlesDrug resistance in ovarian cancer: from the laboratory to the clinic
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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Diurnal cortisol and survival in epithelial ovarian cancer
2015, PsychoneuroendocrinologyCitation Excerpt :Both pathways are biologically plausible. Most ovarian cancer patients respond favorably to front-line treatment and achieve a period of disease remission, however, the development of drug resistant disease in subsequent recurrence is a major factor in survival (Sood and Buller, 1998). Interestingly, a recent study found that breast cancer cell lines incubated with cortisol demonstrated marked resistance to the effects of paclitaxel, a common front-line chemotherapeutic agent in the treatment of ovarian cancer, and this effect was reversed by co-incubation with a glucocorticoid receptor antagonist (Flint et al., 2009).
High claudin-7 expression is associated with a poor response to platinum-based chemotherapy in epithelial ovarian carcinoma
2011, European Journal of CancerCitation Excerpt :Most of EOC cases are advanced at the time of diagnosis and the majority of these patients develop recurrent disease, despite an initial response to primary treatment consisting of surgical debulking and chemotherapy.2 Although EOC is highly responsive to initial platinum-based combination chemotherapy, successful management of advanced or recurrent gynaecologic malignancies is often difficult due to both intrinsic and acquired resistance of cancer cells to cytotoxic drugs.3,4 Therefore, novel strategies that may be effective in enhancing sensitivity or reversing resistance to chemotherapy are urgently needed for those patients with EOCs who either do not respond to initial therapy or develop recurrent disease.
Influence of chemoresistance and p53 status on fluoro-2-deoxy-d-glucose incorporation in cancer
2010, Nuclear Medicine and BiologyNovel strategies for reversing platinum resistance
2009, Drug Resistance UpdatesCitation Excerpt :Epithelial ovarian cancer is initially responsive to platinum-based therapy; however, recurrent disease is often refractory to treatment and is associated with high mortality rates (McGuire et al., 1996; Ozols and Young, 1984; Sood and Buller, 1998).
Is time to chemotherapy a determinant of prognosis in advanced-stage ovarian cancer?
2007, Gynecologic OncologyCitation Excerpt :Although most tumors are chemosensitive when patients first present with disease, the 5-year survival rate is only 30% [17]. Chemotherapy resistance may develop along many pathways [18–20]. Alterations in cellular pharmacology (e.g., reduced medication accumulation), inactivation of cisplatin by sulfur-containing molecules, and enhanced DNA repair may result in resistance to platinum-containing compounds.