Guest Editors
Prof. Fátima Martel
Email: fmartel@med.up.pt
Affiliation: Unit of Biochemistry, Department of Biomedicine, Faculty of Medicine, University of Porto, Porto, Portugal
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Research Interests: cancer cell transport, transmembrane transport mechanisms, epithelial transport of organic compounds, plasma membrane transport of nutrients in cancer cells, modulation of membrane transport by xenobiotics, changes of membrane transport in pathological conditions
Summary
Metabolic remodeling is a key feature of cancer cells. Specifically, cancer cells undergo metabolic remodeling to support rapid proliferation and survival, reprogramming pathways such as glucose, amino acid, and lipid metabolism to sustain biosynthesis, redox balance, and energy production even under nutrient or oxygen limitation. This adaptive rewiring—exemplified by aerobic glycolysis and altered mitochondrial function—also promotes resistance to stress and therapy. As all cancer cells are dependent on this change in metabolism, these altered pathways represent attractive therapeutic targets.
Knowledge of cancer cell metabolic characteristics has greatly expanded since the first observation of abnormal glucose metabolism in cancer cells, the so-called Warburg effect. Currently, a complex set of changes in macronutrient (carbohydrates, amino acids, and lipids) metabolism is known to exist in cancer cells. It is also evident that many of the signaling pathways that are affected by genetic mutations and the tumour microenvironment have a profound effect on cancer cell core metabolism. Moreover, spatial heterogeneity of nutrient availability and metabolic phenotypes exists, allowing metabolic cooperation between different populations of cells within tumors. It is also of note that some anticancer therapy agents (eg. antifolates) target the specific metabolic needs of cancer cells and remain effective agents in the clinic today.
Targeted cancer therapies based on reprogramming nutrient or metabolite metabolism have received substantial attention both conceptually and in clinical practice. Not only it is important to explore the possibility of targeting metabolic dependencies of cancer cells as a selective anticancer strategy, and identifying tumors susceptible to metabolic therapy, but it is also crucial to understand and explore altered metabolic phenotypes of therapy-resistant tumors, relative to treatment-naïve tumors, as a target to overcome cancer resistance to therapy.
Keywords
cancer metabolism, membrane transporters, metabolic enzymes, metabolic pathways, cancer therapy, metabolism in therapy-resistant cancers
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