98%
921
2 minutes
20
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.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8750473 | PMC |
http://dx.doi.org/10.3390/cancers14010191 | DOI Listing |
Front Immunol
September 2025
Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
Immune cell metabolism is essential for regulating immune responses, including activation, differentiation, and function. Through glycolysis and oxidative phosphorylation (OXPHOS), metabolism supplies energy and key intermediates for cell growth and proliferation. Importantly, some metabolites generated during these processes act as signaling molecules that influence immune activity.
View Article and Find Full Text PDFFEBS J
September 2025
Neutron Scattering Division, Oak Ridge National Laboratory, USA.
Serine hydroxymethyltransferase (SHMT) is a critical enzyme in the one-carbon (1C) metabolism pathway catalyzing the reversible conversion of L-Ser into Gly and concurrent transfer of 1C unit to tetrahydrofolate (THF) to give 5,10-methylene-THF (5,10-MTHF), which is used in the downstream syntheses of biomolecules critical for cell proliferation. The cellular 1C metabolism is hijacked by many cancer types to support cancer cell proliferation, making SHMT a promising target for the design and development of novel small-molecule antimetabolite chemotherapies. To advance structure-assisted drug design, knowledge of SHMT catalysis is crucial, but can only be fully realized when the atomic details of each reaction step governed by the acid-base catalysis are elucidated by visualizing active site hydrogen atoms.
View Article and Find Full Text PDFCell Biochem Biophys
September 2025
Laboratório de Sinalização Celular e Expressão Gênica, Instituto de Biociências, Departamento de Biologia Geral e Aplicada, Universidade Estadual Paulista "Júlio de Mesquita Filho" - Campus Rio Claro, Rio Claro, SP, Brazil.
Objectives: Vitamin B12 plays a vital role in folate-mediated one-carbon metabolism (FOCM), a series of one-carbon transfer reactions that generate nucleotides (thymidylate (dTMP) and purines) and methionine. Inadequate levels of B12 impair FOCM, depressing de novo thymidylate (dTMP) synthesis, which in turn leads to uracil accumulation in DNA. This phenomenon has been well documented in nuclear DNA.
View Article and Find Full Text PDFNat Plants
September 2025
Department of Energy Plant Research Laboratory, Michigan State University, East Lansing, MI, USA.
Photorespiration is the second largest carbon flux in most leaves and is integrated into metabolism broadly including one-carbon (C) metabolism. Photorespiratory intermediates such as serine and others may serve as sources of C units, but it is unclear to what degree this happens in vivo, whether altered photorespiration changes flux to C metabolism, and if so through which intermediates. To clarify these questions, we quantified carbon flux from photorespiration to C metabolism using CO labelling and isotopically non-stationary metabolic flux analysis in Arabidopsis thaliana under different O concentrations which modulate photorespiration.
View Article and Find Full Text PDF