Evaluation of Epigenetic Drug Targeting of Heterogenous Tumor Cell Fractions Using Potential Biomarkers of Response in Ovarian Cancer

Abstract Context.—Current tumor markers for ovarian cancer still lack adequate sensitivity and specificity to be applicable in large populations. High-throughput proteomic profiling and bioinformatics tools allow for the rapid screening of a large number of potential biomarkers in serum, plasma, or other body fluids. Objective.—To determine whether protein profiles of plasma can be used to identify potential biomarkers that improve the detection of ovarian cancer. Design.—We analyzed plasma samples that had been collected between 1998 and 2001 from patients with sporadic ovarian serous neoplasms before tumor resection at various International Federation of Gynecology and Obstetrics stages (stage I [n = 11], stage II [n = 3], and stage III [n = 29]) and from women without known neoplastic disease (n = 38) using proteomic profiling and bioinformatics. We compared results between the patients with and without cancer and evaluated their discriminatory performance against that of the cancer antigen 125 (CA125) tumor marker. Results.—We selected 7 biomarkers based on their collective contribution to the separation of the 2 patient groups. Among them, we further purified and subsequently identified 3 biomarkers. Individually, the biomarkers did not perform better than CA125. However, a combination of 4 of the biomarkers significantly improved performance (P ≤ .001). The new biomarkers were complementary to CA125. At a fixed specificity of 94%, an index combining 2 of the biomarkers and CA125 achieves a sensitivity of 94% (95% confidence interval, 85%–100.0%) in contrast to a sensitivity of 81% (95% confidence interval, 68%–95%) for CA125 alone. Conclusions.—The combined use of bioinformatics tools and proteomic profiling provides an effective approach to screen for potential tumor markers. Comparison of plasma profiles from patients with and without known ovarian cancer uncovered a panel of potential biomarkers for detection of ovarian cancer with discriminatory power complementary to that of CA125. Additional studies are required to further validate these biomarkers.

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FIRST-IN-HUMAN PHASE I RESULTS SHOW SAFETY, TOLERABILITY AND BRAIN PENETRANCE OF ORY-2001, AN EPIGENETIC DRUG TARGETING LSD1 AND MAO-B

Alzheimer s & Dementia ◽

10.1016/j.jalz.2017.07.739 ◽

2017 ◽

Vol 13 (7) ◽

pp. P1573-P1574 ◽

Cited By ~ 7

Author(s):

Tamara Maes ◽

Cesar Molinero ◽

Rosa M. Antonijoan ◽

Juan Manuel Ferrero-Cafiero ◽

Joan Martínez-Colomer ◽

...

Keyword(s):

Phase I ◽

Drug Targeting ◽

Mao B ◽

Epigenetic Drug

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Nanocarriers for ovarian cancer active drug targeting

Journal of Drug Delivery Science and Technology ◽

10.1016/s1773-2247(12)50068-7 ◽

2012 ◽

Vol 22 (5) ◽

pp. 421-426 ◽

Cited By ~ 2

Author(s):

F. Delie ◽

E. Allemann ◽

M. Cohen

Keyword(s):

Ovarian Cancer ◽

Drug Targeting ◽

Active Drug

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Improved clinical sensitivity detection of circulating tumor cell assays using a dual selection strategy in women with epithelial ovarian cancer

Gynecologic Oncology ◽

10.1016/j.ygyno.2016.04.364 ◽

2016 ◽

Vol 141 ◽

pp. 138-139

Author(s):

W.Z. Wysham ◽

M.A. Witek ◽

S.A. Soper ◽

P.A. Gehrig ◽

J.E. Stine ◽

...

Keyword(s):

Ovarian Cancer ◽

Tumor Cell ◽

Epithelial Ovarian Cancer ◽

Circulating Tumor Cell ◽

Selection Strategy ◽

Clinical Sensitivity ◽

Cell Assays ◽

Sensitivity Detection

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Comparative Proteomic Analysis of Advanced Ovarian Cancer Tissue to Identify Potential Biomarkers of Responders and Nonresponders to First-Line Chemotherapy of Carboplatin and Paclitaxel

Biomarkers in Cancer ◽

10.4137/bic.s35775 ◽

2016 ◽

Vol 8 ◽

pp. BIC.S35775 ◽

Cited By ~ 5

Author(s):

Urmila Sehrawat ◽

Ruchika Pokhriyal ◽

Ashish Kumar Gupta ◽

Roopa Hariprasad ◽

Mohd Imran Khan ◽

...

Keyword(s):

Ovarian Cancer ◽

Advanced Ovarian Cancer ◽

Spectrometric Analysis ◽

Cancer Tissue ◽

Chemotherapy Response ◽

Tissue Samples ◽

Post Surgery ◽

Dismal Prognosis ◽

Apoptotic Activity ◽

Potential Biomarkers

Conventional treatment for advanced ovarian cancer is an initial debulking surgery followed by chemotherapy combination of carboplatin and paclitaxel. Despite initial high response, three-fourths of these women experience disease recurrence with a dismal prognosis. Patients with advanced-stage ovarian cancer who underwent cytoreductive surgery were enrolled and tissue samples were collected. Post surgery, these patients were started on chemotherapy and followed up till the end of the cycle. Fluorescence-based differential in-gel expression coupled with mass spectrometric analysis was used for discovery phase of experiments, and real-time polymerase chain reaction, Western blotting, and pathway analysis were performed for expression and functional validation of differentially expressed proteins. While aldehyde reductase, hnRNP, cyclophilin A, heat shock protein-27, and actin are upregulated in responders, prohibitin, enoyl-coA hydratase, peroxiredoxin, and fibrin-β are upregulated in the nonresponders. The expressions of some of these proteins correlated with increased apoptotic activity in responders and decreased apoptotic activity in nonresponders. Therefore, the proteins qualify as potential biomarkers to predict chemotherapy response.

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