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High-grade serous ovarian cancer (HGSOC) constitutes the majority of all ovarian cancer cases and has staggering rates of both refractory and recurrent disease. While most patients respond to the initial treatment with paclitaxel and platinum-based drugs, up to 25% do not, and of the remaining that do, 75% experience disease recurrence within the subsequent two years. Intrinsic resistance in refractory cases is driven by environmental stressors like tumor hypoxia which alter the tumor microenvironment to promote cancer progression and resistance to anticancer drugs. Recurrent disease describes the acquisition of chemoresistance whereby cancer cells survive the initial exposure to chemotherapy and develop adaptations to enhance their chances of surviving subsequent treatments. Of the environmental stressors cancer cells endure, exposure to hypoxia has been identified as a potent trigger and priming agent for the development of chemoresistance. Both in the presence of the stress of hypoxia or the therapeutic stress of chemotherapy, cancer cells manage to cope and develop adaptations which prime populations to survive in future stress. One adaptation is the modification in the secretome. Chemoresistance is associated with translational reprogramming for increased protein synthesis, ribosome biogenesis, and vesicle trafficking. This leads to increased production of soluble proteins and extracellular vesicles (EVs) involved in autocrine and paracrine signaling processes. Numerous studies have demonstrated that these factors are largely altered between the secretomes of chemosensitive and chemoresistant patients. Such factors include cytokines, growth factors, EVs, and EV-encapsulated microRNAs (miRNAs), which serve to induce invasive molecular, biophysical, and chemoresistant phenotypes in neighboring normal and cancer cells. This review examines the modifications in the secretome of distinct chemoresistant ovarian cancer cell populations and specific secreted factors, which may serve as candidate biomarkers for aggressive and chemoresistant cancers.
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Models for measuring metabolic chemical changes in the metastasis of high grade serous ovarian cancer: fallopian tube, ovary, and omentum
Abstract Ovarian cancer (OC) is the most lethal gynecologic malignancy and high grade serous ovarian cancer (HGSOC) is the most common and deadly subtype, accounting for 70–80% of OC deaths. HGSOC has a distinct pattern of metastasis as many believe it originates in the fallopian tube and then it metastasizes first to the ovary, and later to the adipose-rich omentum. Metabolomics has been heavily utilized to investigate metabolite changes in HGSOC tumors and metastasis. Generally, metabolomics studies have traditionally been applied to biospecimens from patients or animal models; a number of recent studies have combined metabolomics with innovative cell-culture techniques to model the HGSOC metastatic microenvironment for the investigation of cell-to-cell communication. The purpose of this review is to serve as a tool for researchers aiming to model the metastasis of HGSOC for metabolomics analyses. It will provide a comprehensive overview of current knowledge on the origin and pattern of metastasis of HGSOC and discuss the advantages and limitations of different model systems to help investigators choose the best model for their research goals, with a special emphasis on compatibility with different metabolomics modalities. It will also examine what is presently known about the role of small molecules in the origin and metastasis of HGSOC.
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- Award ID(s):
- 2128044
- PAR ID:
- 10658328
- Publisher / Repository:
- Oxford University Press
- Date Published:
- Journal Name:
- Molecular Omics
- Volume:
- 17
- Issue:
- 6
- ISSN:
- 2515-4184
- Format(s):
- Medium: X Size: p. 819-832
- Size(s):
- p. 819-832
- Sponsoring Org:
- National Science Foundation
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