A chemoresponse assay for prediction of platinum resistance in primary ovarian cancer

Krivak, Thomas C.; Lele, Shashikant; Richard, Scott D.; Secord, Angeles Alvarez; Leath, Charles A.; Brower, Stacey L.; Tian, Chunqiao; Moore, Richard G.

doi:10.1016/j.ajog.2014.02.009

Cited by 18 publications

(16 citation statements)

References 21 publications

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“…This study demonstrates that assay resistance to carboplatin is associated with reduced PFS in EOC patients treated with standard of care carboplatin/paclitaxel, supporting the assay’s ability to identify platinum-resistant patients. Furthermore, of those patients who were resistant to carboplatin in vitro, 59 % of them displayed assay sensitivity (S or IS) to at least one other agent [48]. …”

Section: Chemofxmentioning

confidence: 99%

Overview of a chemoresponse assay in ovarian cancer

Grendys

Fiorica²,

Orr

et al. 2014

Clin Transl Oncol

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The objective of this review is to summarize recent scientific and medical literature regarding chemoresponse assays or chemotherapy sensitivity and resistance assays (CSRAs), specifically as applied to epithelial ovarian cancer. A total of sixty-seven articles, identified through PubMed using the key words “in vitro chemoresponse assay,” “chemo sensitivity resistance assay,” “ATP,” “HDRA,” “EDR,” “MiCK,” and “ChemoFx,” were reviewed. Recent publications on marker validation, including relevant clinical trial designs, were also included. Recent CSRA research and clinical studies are outlined in this review. Published findings demonstrate benefits regarding patient outcome with respect to recent CSRAs. Specifically, analytical and clinical validations, as well as clinical utility and economic benefit, of the most common clinically used CSRA in the United States support its use to aid in making effective, individualized clinical treatment selections for patients with ovarian cancer.

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Section: Chemofxmentioning

confidence: 99%

Overview of a chemoresponse assay in ovarian cancer

Grendys

Fiorica²,

Orr

et al. 2014

Clin Transl Oncol

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“…The poor prognosis of epithelial ovarian cancer (EOC) is due to a combination of the aggressive characteristics of the disease and an unpredictable response to front-line therapy, further compounded by late detection of the disease and resistance of ovarian cancers to current treatments (3). The primary treatment for EOC consists of aggressive cytoreductive surgery, followed by chemotherapy with platinum and taxane (4). Although platinum and taxane combination remains the standard treatment for EOC, new drug combinations (5) as well as different administration schedules (6) are being tested and might be reasonable options for first-line treatment of women with advanced EOC.…”

Section: Introductionmentioning

confidence: 99%

Effect of Pantethine on Ovarian Tumor Progression and Choline Metabolism

Penet¹,

Krishnamachary²,

Wildes³

et al. 2016

Front. Oncol.

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Epithelial ovarian cancer remains the leading cause of death from gynecologic malignancy among women in developed countries. New therapeutic strategies evaluated with relevant preclinical models are urgently needed to improve survival rates. Here, we have assessed the effect of pantethine on tumor growth and metabolism using magnetic resonance imaging and high-resolution proton magnetic resonance spectroscopy (MRS) in a model of ovarian cancer. To evaluate treatment strategies, it is important to use models that closely mimic tumor growth in humans. Therefore, we used an orthotopic model of ovarian cancer where a piece of tumor tissue, derived from an ovarian tumor xenograft, is engrafted directly onto the ovary of female mice, to maintain the tumor physiological environment. Treatment with pantethine, the precursor of vitamin B5 and active moiety of coenzyme A, was started when tumors were ~100 mm3 and consisted of a daily i.p. injection of 750 mg/kg in saline. Under these conditions, no side effects were observed. High-resolution 1H MRS was performed on treated and control tumor extracts. A dual-phase extraction method based on methanol/chloroform/water was used to obtain lipid and water-soluble fractions from the tumors. We also investigated effects on metastases and ascites formation. Pantethine treatment resulted in slower tumor progression, decreased levels of phosphocholine and phosphatidylcholine, and reduced metastases and ascites occurrence. In conclusion, pantethine represents a novel potential, well-tolerated, therapeutic tool in patients with ovarian cancer. Further in vivo preclinical studies are needed to confirm the beneficial role of pantethine and to better understand its mechanism of action.

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“…Krivak and colleagues reported that in vitro assay resistance to carboplatin is associated with decreased PFS in women with advanced-stage EOC treated with platinum based therapy. Specifically, women whose tumor specimens demonstrated in vitro platinum resistance were at higher risk for disease progression compared to those with sensitive or intermediate sensitive assay results (median PFS: 11.8 vs 16.6 months, respectively, P < .001) [6]. In addition, our group compared in vitro assay response between Type I and Type II EOC and found that, despite the dogmatic belief that Type I EOC are chemoresistant, the majority (86%) of Type I tumors were chemosensitive to at least one cytotoxic agent and 35.7% were pan-S to all 7 agents tested [14].…”

Section: Discussionmentioning

confidence: 99%

“…Details regarding the particular chemoresponse assay used in this study (ChemoFx®, Helomics Corporation, Pittsburgh, PA) have been described elsewhere [6, 7]. Assay preparation included an immunocytochemistry step to aid in the confirmation that cells were of epithelial, rather than stromal, origin.…”

Section: Methodsmentioning

confidence: 99%

Analysis of in vitro chemoresponse assays in endometrioid endometrial adenocarcinoma: an observational ancillary analysis

Davidson

Foote

Brower³

et al. 2016

gynaecol oncol res pract

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BackgroundChemotherapy plays a role in the treatment of endometrioid endometrial cancer (EEC); however, tumor grade may affect response. Our objective was to evaluate associations between tumor grade and in vitro chemoresponse.MethodsWe conducted an analysis of primary tumor samples from women with EEC undergoing in vitro chemoresponse testing. Results were classified as sensitive (S), intermediate (I), or resistant (R) to each drug tested. Correlations between tumor grade and response were examined.ResultsData was collected from 159 patients: 28 with grade 1 (18%), 52 with grade 2 (32%), and 79 (50%) with grade 3 tumors. Median age of patients was 62 (range 31–92). Most patients were Caucasian (83%) with advanced disease (Stage III: 50.9%; Stage IV: 13.2%). Overall chemoresponse was similar across all grades. Fifty percent, 56 and 51% for grade 1, 2, and 3 tumors, respectively, demonstrated S results to at least 1 agent. There was no association between grade and in vitro response to chemotherapy agents (p > 0.05) except a marginal association between grade and doxorubicin response (p = 0.08). Grade 1 and 2 cancers were more likely to demonstrate R results for doxorubicin compared to grade 3 cancers (G1: 19% vs G2: 25% vs G3: 8%; p = 0.08). In a subset tested for all 7 agents, only one patient tumor was pan-R and 4 were pan-S.ConclusionsBased on our data, grades 1–3 EEC have similar in vitro chemoresponse. These findings suggest that chemotherapy may be useful in advanced low grade EECs, but further clinical correlation is needed.

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A chemoresponse assay for prediction of platinum resistance in primary ovarian cancer

Cited by 18 publications

References 21 publications

Overview of a chemoresponse assay in ovarian cancer

Overview of a chemoresponse assay in ovarian cancer

Effect of Pantethine on Ovarian Tumor Progression and Choline Metabolism

Analysis of in vitro chemoresponse assays in endometrioid endometrial adenocarcinoma: an observational ancillary analysis

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