Sphingolipid metabolism and drug resistance in ovarian cancer

Kreitzburg, Kelly M.; Waardenburg, Robert C.A.M. van; Yoon, Karina J.

doi:10.20517/cdr.2018.06

Cited by 17 publications

(21 citation statements)

References 138 publications

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“…In fact, a resensitization to paclitaxel of taxane-resistant SKOV3.TR ovarian cancer cells have been shown with the combination of paclitaxel with C6-ceramide-encapsulated in poly(ethylene oxide)-modified poly(epsilon-caprolactone) (PEO-PCL) nanoparticles (235). Kelly M. and colleagues demonstrated that the combined treatment of tamoxifen with the Sphingosine kinase 1 (SK1) inhibitor FTY720 blocks proliferation of both ERα-positive and ERα-negative drug-resistant cell lines and an ERα-positive PDX model of ovarian tumor (240). The multiple mechanisms of action of tamoxifen and its relatively high therapeutic index provide a strong rationale for combining tamoxifen with FTY720, as a strategy for treating ovarian tumors and circumventing drug resistance (226,(241)(242)(243).…”

Section: Targeting Lipid Metabolismmentioning

confidence: 99%

Metabolic Plasticity in Chemotherapy Resistance

et al. 2020

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Resistance of cancer cells to chemotherapy is the first cause of cancer-associated death. Thus, new strategies to deal with the evasion of drug response and to improve clinical outcomes are needed. Genetic and epigenetic mechanisms associated with uncontrolled cell growth result in metabolism reprogramming. Cancer cells enhance anabolic pathways and acquire the ability to use different carbon sources besides glucose. An oxygen and nutrient-poor tumor microenvironment determines metabolic interactions among normal cells, cancer cells and the immune system giving rise to metabolically heterogeneous tumors which will partially respond to metabolic therapy. Here we go into the best-known cancer metabolic profiles and discuss several studies that reported tumors sensitization to chemotherapy by modulating metabolic pathways. Uncovering metabolic dependencies across different chemotherapy treatments could help to rationalize the use of metabolic modulators to overcome therapy resistance.

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Section: Targeting Lipid Metabolismmentioning

confidence: 99%

Metabolic Plasticity in Chemotherapy Resistance

et al. 2020

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“…Downregulation of SphK2 with siRNA inhibited proliferation of glioblastoma cells more potently than that observed for SphK1 knockdown (van Brocklyn et al, ), suggesting that SphK2 is a more viable candidate for chemotherapeutic targeting. Based on previous studies, SphK2 has the differential ability to be involved in either extrinsic or intrinsic pathway of apoptosis, depending on the type of cell line studied, presence or absence of serum, growth factors and glucose, the type of chemotherapeutic/agent used, as well as other stressors such as hypoxia (Kreitzburg et al, ; Mizutani et al, ; Okada et al, ).…”

Section: Development Of Resistance By Sphk2 Via Aberrant Regulation Omentioning

confidence: 99%

New insights into the roles and regulation of SphK2 as a therapeutic target in cancer chemoresistance

Hasanifard

Sheervalilou

Majidinia

et al. 2018

Journal Cellular Physiology

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Chemoresistance is a complicated process developed by most cancers and accounts for the majority of relapse and metastasis in cancer. The main mechanisms of chemoresistance phenotype include increased expression and/or activated drug efflux pumps, altered DNA repair, altered metabolism of therapeutics as well as impaired apoptotic signaling pathways. Aberrant sphingolipid signaling has also recently received considerable attention in chemoresistance. Sphingolipid metabolites regulate main biological processes such as apoptosis, cell survival, proliferation, and differentiation. Two sphingosine kinases, SphK1 and SphK2, convert sphingosine to sphingosine‐1‐phosphate, an antiapoptotic bioactive lipid mediator. Numerous evidence has revealed the involvement of activated SphK1 in tumorigenesis and resistance, however, contradictory results have been found for the role of SphK2 in these functions. In some studies, overexpression of SphK2 suppressed cell growth and induced apoptosis. In contrast, some others have shown cell proliferation and tumor promotion effect for SphK2. Our understanding of the role of SphK2 in cancer does not have a sufficient integrity. The main focus of this review will be on the re‐evaluation of the role of SphK2 in cell death and chemoresistance in light of our new understanding of molecular targeted therapy. We will also highlight the connections between SphK2 and the DNA damage response. Finally, we will provide our insight into the regulatory mechanisms of SphKs by two main categories, micro and long, noncoding RNAs as the novel players of cancer chemoresistance.

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“…SM consists of a phosphocholine head group and ceramide contained sphingosine and fatty acids and its subcellular location is correlated with cholesterol [ 91 ]. It is important to acquire a resistance to anticancer agents since ovarian cancer cells provoke an aberrant SM mechanism that involves the promotion of the catabolism of ceramide, and the production and accumulation of ceramide [ 92 , 93 ].…”

Section: Discussionmentioning

confidence: 99%

Convergence of Plasma Metabolomics and Proteomics Analysis to Discover Signatures of High-Grade Serous Ovarian Cancer

Ahn

Yeom

et al. 2020

Cancers

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The 5-year survival rate in the early and late stages of ovarian cancer differs by 63%. In addition, a liquid biopsy is necessary because there are no symptoms in the early stage and tissue collection is difficult without using invasive methods. Therefore, there is a need for biomarkers to achieve this goal. In this study, we found blood-based metabolite or protein biomarker candidates for the diagnosis of ovarian cancer in the 20 clinical samples (10 ovarian cancer patients and 10 healthy control subjects). Plasma metabolites and proteins were measured and quantified using mass spectrometry in ovarian cancer patients and control groups. We identified the differential abundant biomolecules (34 metabolites and 197 proteins) and statistically integrated molecules of different dimensions to better understand ovarian cancer signal transduction and to identify novel biological mechanisms. In addition, the biomarker reliability was verified through comparison with existing research results. Integrated analysis of metabolome and proteome identified emerging properties difficult to grasp with the single omics approach, more reliably interpreted the cancer signaling pathway, and explored new drug targets. Especially, through this analysis, proteins (PPCS, PMP2, and TUBB) and metabolites (L-carnitine and PC-O (30:0)) related to the carnitine system involved in cancer plasticity were identified.

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Sphingolipid metabolism and drug resistance in ovarian cancer

Cited by 17 publications

References 138 publications

Metabolic Plasticity in Chemotherapy Resistance

Metabolic Plasticity in Chemotherapy Resistance

New insights into the roles and regulation of SphK2 as a therapeutic target in cancer chemoresistance

Convergence of Plasma Metabolomics and Proteomics Analysis to Discover Signatures of High-Grade Serous Ovarian Cancer

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