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

DOI

10.3390/cancers14010191

Authors

Adrianne Wallace-Povirk, Molecular Therapeutics Program, Barbara Ann Karmanos Cancer Institute, 421 East Canfield Street, Detroit, MI 48201, USA.
Zhanjun Hou, Molecular Therapeutics Program, Barbara Ann Karmanos Cancer Institute, 421 East Canfield Street, Detroit, MI 48201, USA.
Md Junayed Nayeen, Division of Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA 15282, USA.
Aleem Gangjee, Division of Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA 15282, USA.
Larry H. Matherly, Molecular Therapeutics Program, Barbara Ann Karmanos Cancer Institute, 421 East Canfield Street, Detroit, MI 48201, USA.

Document Type

Journal Article

Publication Date

12-31-2021

Publication Title

Cancers

Volume

14

Issue

1

ISSN

2072-6694

Keywords

epithelial ovarian cancer, folate, folate receptor, folate transport, one-carbon metabolism, proton-coupled folate transporter, tumor microenvironment

Abstract

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.

Open Access

Gold

Repository Citation

Wallace-Povirk, A., Hou, Z., Nayeen, M. J., Gangjee, A., & Matherly, L. H. (2021). Folate Transport and One-Carbon Metabolism in Targeted Therapies of Epithelial Ovarian Cancer. Cancers, 14 (1). https://doi.org/10.3390/cancers14010191