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Malignant Ascites in Ovarian Cancer: Cellular, Acellular, and Biophysical Determinants of Molecular Characteristics and Therapy Response

期刊

CANCERS
卷 13, 期 17, 页码 -

出版社

MDPI
DOI: 10.3390/cancers13174318

关键词

malignant ascites; epithelial ovarian cancer; chemoresistance; mechanical stress; flow-induced shear stress; photodynamic therapy; tumor microenvironment; transcoelomic metastases; tumor heterogeneity; epithelial to mesenchymal transition

类别

资金

  1. National Institute of Environmental Health Sciences, National Institutes of Health (NIH) [T32 ES007126]
  2. NIH [R00CA175292, UL1TR002489, R01 EB029805, R33CA204582, U01CA202177, R00CA194269]
  3. National Center for Advancing Translational Sciences (NCATS), NIH [UL1TR002489]
  4. UNC-NC State Joint Department of Biomedical Engineering Start-up Fund
  5. National Science Foundation [CMMI- 1929412]
  6. UNC-NC State Joint BME Department Start-up Fund
  7. UMD Start-up Fund
  8. UMD-UMB 2018 Research and Innovation Seed Grant
  9. Caring Together, NY, Ovarian Cancer Research grant
  10. UMD-NCI Partnership for Integrative Cancer Research Grant
  11. UD-DoD grants [LC150650, W81XWH-16-1-0200, LC19029, W81XWH-20-1-0746]
  12. NCI Center for Cancer Nano-technology Excellence for Translational Diagnostics [NCI- U54CA199075]
  13. Canary Center at Stanford for Cancer Early Detection Seed Award

向作者/读者索取更多资源

The abnormal accumulation of fluid in the abdomen, known as ascites, often indicates underlying tissue dysfunction or disease, such as cancer. Among ovarian cancer patients, the presence of ascites is associated with the poorest outcomes. Despite limited understanding of the role of malignant ascites in promoting metastasis and therapy resistance, treatment options are being explored to improve patient prognosis.
Simple Summary Accumulation of excess fluid in the abdomen typically indicates abnormal function or disease, such as cancer, in the underlying tissues. This accumulation of fluid, or ascites, occurs more frequently in patients with advanced-stage ovarian cancer than any other type of cancer. The presence of ascites indicates the poorest outcomes for patients with advanced stage ovarian cancer, but little is known about the reasons for these dismal outcomes. This review discusses the current understanding of ascites, starting with an overview of ovarian cancer and ascites, followed by a description of the tools used to analyze the components of ascites and how these components modulate ovarian cancer biology. A perspective on the mechanical effects of ascites and the impact of mechanical stress on treatment resistance is provided. Lastly, treatment options for ascites and opportunities to develop new therapeutic strategies to improve outcomes are discussed. Ascites refers to the abnormal accumulation of fluid in the peritoneum resulting from an underlying pathology, such as metastatic cancer. Among all cancers, advanced-stage epithelial ovarian cancer is most frequently associated with the production of malignant ascites and is the leading cause of death from gynecologic malignancies. Despite decades of evidence showing that the accumulation of peritoneal fluid portends the poorest outcomes for cancer patients, the role of malignant ascites in promoting metastasis and therapy resistance remains poorly understood. This review summarizes the current understanding of malignant ascites, with a focus on ovarian cancer. The first section provides an overview of heterogeneity in ovarian cancer and the pathophysiology of malignant ascites. Next, analytical methods used to characterize the cellular and acellular components of malignant ascites, as well the role of these components in modulating cell biology, are discussed. The review then provides a perspective on the pressures and forces that tumors are subjected to in the presence of malignant ascites and the impact of physical stress on therapy resistance. Treatment options for malignant ascites, including surgical, pharmacological and photochemical interventions are then discussed to highlight challenges and opportunities at the interface of drug discovery, device development and physical sciences in oncology.

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