Related Experiment Video
Updated: Dec 31, 2025
Assessment of Ovarian Cancer Spheroid Attachment and Invasion of Mesothelial Cells in Real Time
Published on: May 20, 2014
Sphingolipid metabolism and drug resistance in ovarian cancer
Kelly M Kreitzburg1, Robert C A M van Waardenburg1, Karina J Yoon1
1Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Abstract:
Despite progress in understanding molecular aberrations that contribute to the development and progression of ovarian cancer, virtually all patients succumb to drug resistant disease at relapse. Emerging data implicate bioactive sphingolipids and regulation of sphingolipid metabolism as components of response to chemotherapy or development of resistance. Increases in cytosolic ceramide induce apoptosis in response to therapy with multiple classes of chemotherapeutic agents. Aberrations in sphingolipid metabolism that accelerate the catabolism of ceramide or that prevent the production and accumulation of ceramide contribute to resistance to standard of care platinum- and taxane-based agents. The aim of this review is to highlight current literature and research investigating the influence of the sphingolipids and enzymes that comprise the sphingosine-1-phosphate pathway on the progression of ovarian cancer. The focus of the review is on the utility of sphingolipid-centric therapeutics as a mechanism to circumvent drug resistance in this tumor type.
Insights
Drug resistance in ovarian cancer is a major challenge. This review explores how sphingolipids and their metabolism impact chemotherapy response and resistance, suggesting sphingolipid-targeted therapies to overcome treatment failure.
Area of Science:
- Oncology
- Biochemistry
- Pharmacology
Background:
- Ovarian cancer relapse is often due to drug-resistant disease despite advances in understanding molecular drivers.
- Bioactive sphingolipids and their metabolic regulation are increasingly recognized as key factors in chemotherapy response and resistance.
- Elevated cytosolic ceramide levels can sensitize ovarian cancer cells to chemotherapy-induced apoptosis.
Purpose of the Study:
- To review current literature on the role of sphingolipids and the sphingosine-1-phosphate pathway in ovarian cancer progression.
- To explore the potential of sphingolipid-centric therapeutics to overcome drug resistance in ovarian cancer.
Main Methods:
- Literature review of preclinical and clinical studies.
- Analysis of research on sphingolipid metabolism and its enzymes.
- Investigation of the sphingosine-1-phosphate pathway in ovarian cancer.
Main Results:
- Aberrations in sphingolipid metabolism, such as accelerated ceramide catabolism or impaired ceramide production, are linked to resistance against platinum and taxane agents.
- Dysregulation of the sphingosine-1-phosphate pathway influences ovarian cancer progression and chemoresistance.
Conclusions:
- Targeting sphingolipid metabolism presents a promising strategy to circumvent drug resistance in ovarian cancer.
- Sphingolipid-centric therapeutics offer a novel approach to improve treatment outcomes for patients with relapsed ovarian cancer.
