In vitro extreme drug resistance assay to taxanes or platinum compounds for the prediction of clinical outcomes in epithelial ovarian cancer: a prospective cohort study

Kim, Hee Seung; Kim, Tae Joong; Chung, Hyun Hoon; Kim, Jae Weon; Kim, Byung Gie; Park, Noh Hyun; Song, Yong Sang; Bae, Duk Soo; Kang, Soon Beom

doi:10.1007/s00432-009-0598-0

Cited by 18 publications

(15 citation statements)

References 28 publications

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“…However, the extensive application of cisplatin may result in adverse gastrointestinal toxicity, including severe nausea and vomiting, renal toxicity and neurotoxicity (13). Notably, long-term use of cisplatin results in drug resistance, which is a major obstacle in cancer chemotherapy (14)(15)(16). Investigation into therapeutic strategies with increased efficacy in order to decrease the side effects of treatment or reduce drug resistance in ovarian cancer is required.…”

Section: Introductionmentioning

confidence: 99%

Oridonin effectively reverses cisplatin drug resistance in human ovarian cancer cells via induction of cell apoptosis and inhibition of matrix metalloproteinase expression

Tan

et al. 2016

Molecular Medicine Reports

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Section: Introductionmentioning

confidence: 99%

Oridonin effectively reverses cisplatin drug resistance in human ovarian cancer cells via induction of cell apoptosis and inhibition of matrix metalloproteinase expression

Tan

et al. 2016

Molecular Medicine Reports

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“…According to the Gynecologic Oncology Group and EuropeanCanadian investigators, platinum-and taxane-based chemotherapy after surgery has been considered as the effective treatment regimen against ovarian cancer [33] with 60% to 80% in overall response rate. However, among the relapsed patients response rate decreased to 15% to 35% to the same treatment regimen [34].…”

Section: Important Clinicopathologic and Genetic Alterationsmentioning

confidence: 99%

Anticancer Strategy Targeting Mitochondrial Biogenesis in Ovarian Cancer

Uddin¹,

Kim²,

Suh³

et al. 2014

J Cancer Sci Ther

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IntroductionOvarian cancer is the most lethal gynecologic malignancy worldwide typically in the post-menopausal women and 5 th leading cause of death in the United States [1][2][3]. About 80% of women are diagnosed at the advanced-stage of disease and have poor prognosis. The 5-year overall survival rate is 45% or below [4][5][6]. Despite the first complete response after the front-line platinum-based chemotherapeutic drugs [7,8], approximately 25% patients suffer from relapse within 6 months who are thought, by definition, to have a chemoresistance [9][10][11][12]. Combination of platinum and other drugs might improve the survival rate [13], but is not out of the danger of additive toxicity [14].Several genetic alterations have been observed in ovarian cancer, involving deactivation mutations in tumor suppressor genes, such as p53, BRCA1 and BRCA2, and activation mutation and/or amplification of proto-oncogenes, like c-MYC, KRAS and AKT [15]. Recent genomic analysis of The Cancer Genome Atlas reported mutations in p53 gene in 96% of 316 cases of high-grade ovarian serous carcinoma (HGOSC) [16]. Other important genetic changes affect phosphatidyinositol-3-kinase (PI3K)-AKT-mammalian target of rapamycin (mTOR) cascade. The mTOR plays a central role in energy metabolism, cell growth/division through macromolecular synthesis and is found to be activated in ovarian cancer [6], which indicates a close relationship between genetic alteration and energy metabolism. It was observed that hexokinase (HK) II, the rate limiting initial enzyme in glycolysis, is overexpressed in ovarian cancer [12]. The genetic alterations and subsequent metabolic remodeling have been found to be associated with the chemoresistance [17], such as association of rictor (mTORC2 component) with resistance to cisplatin [2]. Cisplatin-induced caspase activation causing PTEN cleavage has also been reported as a potential mechanism of chemoresistance in ovarian cancer [18].Mitochondria is a well-adapted endosymbiotic intracellular organelles, became efficient for energy production through-out the course of evolution [19]. They are critical for survival and proliferation of living organisms under aerobic conditions and produce ATP through oxidative phosphorylation (OXPHOS) [20]. Beyond the conventional function they have crucial role in certain neurodegenerative diseases and cancer [21][22][23]. Cellular proliferation largely depends on mitochondrial amount, governed by the process of MtBIO [20]. MtBIO is the production of daughter mitochondria usually from previously existed one through a division process of called fission, subsequent growth, and maintenance by fusion and autophagy of mitochondria (mitophagy) [24]. Currently it has been observed that MtBIO is associated with cancer chemoresistance [25,26] through the modulation of associated proteins such as methylation-controlled J-protein (MCJ, also known as DNAJC15) [25,27], prohibitin 1 (PHB-1) [28][29][30], myeloid cell leukemia sequence 1 (MCL-1) [31,32] etc. in ovarian cancer. Thus it can be s...

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“…Thereby, the treatment of a patient with a toxic agent that does not result in a therapeutic benefit can be prevented (Tattersall & Harnett, 1986; Myers et al, 1987; Beck, 1987). It is known that the capability to predict drug resistance is presumably >95% whereas the ability to predict chemo-sensitivity lies around 60% (Kim et al, 2009). The CTR-Test shows a >99% accuracy in finding ineffective chemotherapeutics that do not produce a clinical response (Kern & Weisenthal, 1990).…”

Section: Introductionmentioning

confidence: 99%

New in vitro system to predict chemotherapeutic efficacy of drug combinations in fresh tumor samples

Kischkel

Eich

Meyer

et al. 2017

PeerJ

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BackgroundTo find the best individual chemotherapy for cancer patients, the efficacy of different chemotherapeutic drugs can be predicted by pretesting tumor samples in vitro via the chemotherapy-resistance (CTR)-Test®. Although drug combinations are widely used among cancer therapy, so far only single drugs are tested by this and other tests. However, several first line chemotherapies are combining two or more chemotherapeutics, leading to the necessity of drug combination testing methods.MethodsWe established a system to measure and predict the efficacy of chemotherapeutic drug combinations with the help of the Loewe additivity concept in combination with the CTR-test. A combination is measured by using half of the monotherapy’s concentration of both drugs simultaneously. With this method, the efficacy of a combination can also be calculated based on single drug measurements.ResultsThe established system was tested on a data set of ovarian carcinoma samples using the combination carboplatin and paclitaxel and confirmed by using other tumor species and chemotherapeutics. Comparing the measured and the calculated values of the combination testings revealed a high correlation. Additionally, in 70% of the cases the measured and the calculated values lead to the same chemotherapeutic resistance category of the tumor.ConclusionOur data suggest that the best drug combination consists of the most efficient single drugs and the worst drug combination of the least efficient single drugs. Our results showed that single measurements are sufficient to predict combinations in specific cases but there are exceptions in which it is necessary to measure combinations, which is possible with the presented system.

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In vitro extreme drug resistance assay to taxanes or platinum compounds for the prediction of clinical outcomes in epithelial ovarian cancer: a prospective cohort study

Abstract: In vitro EDR assay to taxanes and platinum compounds may be helpful for predicting drug response, platinum-resistance and survival in patients with EOC who received taxane- and platinum-based chemotherapy after staging laparotomy.

Cited by 18 publications

References 28 publications

Oridonin effectively reverses cisplatin drug resistance in human ovarian cancer cells via induction of cell apoptosis and inhibition of matrix metalloproteinase expression

Oridonin effectively reverses cisplatin drug resistance in human ovarian cancer cells via induction of cell apoptosis and inhibition of matrix metalloproteinase expression

Anticancer Strategy Targeting Mitochondrial Biogenesis in Ovarian Cancer

New in vitro system to predict chemotherapeutic efficacy of drug combinations in fresh tumor samples

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