scholarly journals Folate Transport and One-Carbon Metabolism in Targeted Therapies of Epithelial Ovarian Cancer

Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 191
Author(s):  
Adrianne Wallace-Povirk ◽  
Zhanjun Hou ◽  
Md. Junayed Nayeen ◽  
Aleem Gangjee ◽  
Larry H. Matherly
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Targeted Therapies ◽  
Folate Receptor ◽  
Gynecologic Malignancy ◽  
Folate Transport ◽  
New Developments ◽  
C1 Metabolism ◽  
Selective Delivery ◽  
One Carbon Metabolism

New therapies are urgently needed for epithelial ovarian cancer (EOC), the most lethal gynecologic malignancy. To identify new approaches for targeting EOC, metabolic vulnerabilities must be discovered and strategies for the selective delivery of therapeutic agents must be established. Folate receptor (FR) α and the proton-coupled folate transporter (PCFT) are expressed in the majority of EOCs. FRβ is expressed on tumor-associated macrophages, a major infiltrating immune population in EOC. One-carbon (C1) metabolism is partitioned between the cytosol and mitochondria and is important for the synthesis of nucleotides, amino acids, glutathione, and other critical metabolites. Novel inhibitors are being developed with the potential for therapeutic targeting of tumors via FRs and the PCFT, as well as for inhibiting C1 metabolism. In this review, we summarize these exciting new developments in targeted therapies for both tumors and the tumor microenvironment in EOC.

scholarly journals One-Carbon Metabolism: Biological Players in Epithelial Ovarian Cancer

2018 ◽  
Vol 19 (7) ◽  
pp. 2092 ◽  
Author(s):  
Andrea Rizzo ◽  
Alessandra Napoli ◽  
Francesca Roggiani ◽  
Antonella Tomassetti ◽  
Marina Bagnoli ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Carbon Metabolism ◽  
Current Knowledge ◽  
Folate Receptor ◽  
Redox Status ◽  
Nucleotide Biosynthesis ◽  
Gynecological Malignancy ◽  
One Carbon Metabolism ◽  
Cell Redox Status

Metabolism is deeply involved in cell behavior and homeostasis maintenance, with metabolites acting as molecular intermediates to modulate cellular functions. In particular, one-carbon metabolism is a key biochemical pathway necessary to provide carbon units required for critical processes, including nucleotide biosynthesis, epigenetic methylation, and cell redox-status regulation. It is, therefore, not surprising that alterations in this pathway may acquire fundamental importance in cancer onset and progression. Two of the major actors in one-carbon metabolism, folate and choline, play a key role in the pathobiology of epithelial ovarian cancer (EOC), the deadliest gynecological malignancy. EOC is characterized by a cholinic phenotype sustained via increased activity of choline kinase alpha, and via membrane overexpression of the alpha isoform of the folate receptor (FRα), both of which are known to contribute to generating regulatory signals that support EOC cell aggressiveness and proliferation. Here, we describe in detail the main biological processes associated with one-carbon metabolism, and the current knowledge about its role in EOC. Moreover, since the cholinic phenotype and FRα overexpression are unique properties of tumor cells, but not of normal cells, they can be considered attractive targets for the development of therapeutic approaches.

scholarly journals Targeted Therapies in Epithelial Ovarian Cancer

Cancers ◽  
2010 ◽  
Vol 2 (1) ◽  
pp. 88-113 ◽  
Author(s):  
Emma Dean ◽  
Loaie El-Helw ◽  
Jurjees Hasan
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Targeted Therapies

scholarly journals Fischer 344 Rat: A Preclinical Model for Epithelial Ovarian Cancer Folate-Targeted Therapy

2015 ◽  
Vol 25 (7) ◽  
pp. 1194-1200 ◽  
Author(s):  
Henri Azaïs ◽  
Gurvan Queniat ◽  
Caroline Bonner ◽  
Olivier Kerdraon ◽  
Meryem Tardivel ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Peritoneal Carcinomatosis ◽  
Cancer Cell ◽  
Targeted Therapies ◽  
Ovarian Cancer Cell ◽  
Preclinical Model ◽  
Fischer 344 ◽  
Fischer 344 Rat

ObjectiveOvarian cancer prognosis remains dire after primary therapy. Recurrence rates are disappointingly high as 60% of women with advanced epithelial ovarian cancer considered in remission will develop recurrent disease within 5 years. Special attention to undetected peritoneal metastasis and residual tumorous cells during surgery is necessary as they are the main predictive factors of recurrences. Folate receptor α (FRα) shows promising prospects in targeting ovarian cancerous cells. Our aim was to determine if the Fischer model described by Rose et al could be used to evaluate folate-targeted therapies in preclinical studies.MethodsNuTu-19 epithelial ovarian cancer cell line was used to induce peritoneal carcinomatosis in female Fischer 344 rats. FRα expression by NuTu-19 cells was assessed in vitro by immunofluorescence using “Cytospin®” protocol. In vitro folate-targeted compound uptake by NuTu-19 cells was evaluated by incubation of FRα-positive ovarian cancer cell lines (NuTu-19/SKOV-3/OVCAR-3/IGROV-1) with or without (control) a folate-targeted photosensitizer. Intracellular incorporation was assessed by confocal microscopy. Determination of in vivo FRα tissue expression by several organs of the peritoneal cavity was studied by immunohistochemistry.ResultsNuTu-19 cells express FRα which allows intracellular incorporation of folate-targeted compound by endocytosis. FRα is expressed in tumor tissue, ovary, and liver. Peritoneum, colon, small intestine, and kidney do not express the receptor.ConclusionsFemale Fischer 344 rat is an inexpensive reproducible and efficient preclinical model to study ovarian peritoneal carcinomatosis folate-targeted therapies.

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