Vitamins are vital nutrients essential for metabolism, functioning as coenzymes, antioxidants, and regulators of gene expression. Their absorption and metabolism rely on specialized transport proteins that ensure bioavailability and cellular utilization. Water-soluble vitamins, including B-complex and vitamin C, are transported by solute carrier (SLC) family proteins and ATP-binding cassette (ABC) transporters for efficient uptake and cellular distribution. Fat-soluble vitamins (A, D, E, and K) rely on lipid-mediated pathways through proteins like scavenger receptor class B type I (SR-BI), CD36, and Niemann-Pick C1-like 1 (NPC1L1), integrating their absorption with lipid metabolism. Defective vitamin transporters are associated with diverse metabolic disorders, including neurological, hematological, and mitochondrial diseases. Advances in structural and functional studies of vitamin transporters highlight their tissue-specific roles and regulatory mechanisms, shedding light on their impact on health and disease. This review emphasizes the significance of vitamin transporters and their potential as therapeutic targets for deficiencies and related chronic conditions.

Personalized medicine holds great promise for treating the underlying causes of many human diseases with high precision. Low-dimensional carbon-based materials are being designed to more closely match specific delivery efficiency for targeted cancer treatment, while enabling the benefits of increased biocompatibility, high cargo-loading capacity and excellent light-responsive properties, including photoluminescence and photothermal effects. Here, we report an unprecedented example of glucose-based carbon-nanodots (CDs-gluc) obtained via a one-pot thermal process from glucose, without using organic solvent and additional reagents. The CDs-gluc nanostructures, composed of a C-sp2 inner core and a glucose outer shell, showed a high photothermal conversion efficiency (η = 42.7 % at 532 nm), good photoluminescence quantum yield (ϕPL = 6 %), and low cytotoxicity. Measurements of cellular Zeta-potential demonstrated the effective interaction of CDs-gluc with the surface of cancer cells overexpressing the Glucose Transporter Type 2 (GLUT2). The effective and specific GLUT2-mediated internalization mechanism was demonstrated by inducing up- and down-regulation of the transporter expression under conditions of glucose excess and deprivation, through fluorescence correlation spectroscopy. The potential of the CDs-gluc as drug nanocarriers was demonstrated by entrapping the anticancer drug 5-fluorouracil, achieving a drug loading capacity of 4.5 ± 0.8 %. In vitro experiments confirmed the excellent light-triggered cell damage activity and remarkable cell-targeting ability of CDs-gluc driven by GLUT2 expression. The easy and green preparation, biocompatibility, effective and specific cellular uptake, photoluminescence and hyperthermia make CDs-gluc appealing candidates in the research of novel nanostructures for cancer cell targeting.

Detection of glucose transporter 4 (GLUT4) is essential for understanding various physiological and pathological processes. This work reports the development of a novel electrochemical immunosensor for the direct detection of GLUT4, employing dissolved oxygen as a redox probe. This molecular oxygen-sensitive response is mediated by a redox-conductive polymer based on thionine. The sensor platform was fabricated via a one-step electropolymerization of thionine and gold nanoparticles (AuNPs) onto a platinum screen-printed electrode (Olean-Oliveira et al., 2022a). The immunosensor was then constructed by physical adsorption of a GLUT4 antibody onto the poly(thionine)-AuNP composite surface. This label-free approach eliminates the need for secondary antibodies or enzymes. The immunosensor performance was evaluated using electrochemical impedance spectroscopy (EIS). The sensing mechanism relies on impedance changes; increasing GLUT4 concentrations lead to increased impedance due to enhanced surface blocking upon GLUT4-antibody binding. This interaction impedes oxygen diffusion to the polymer redox sites, resulting in increased electrical resistance. Analysis of the redox capacitance as a function of frequency demonstrates a decrease in the capacitive arc with increasing GLUT4 concentration.

This research is focused on the metabolomics and cytotoxic effects of the anticancer drug erlotinib encapsulated in poly(lactide-co-glycolide) nanoparticles on non-small cell lung cancer (NSCLC) cell lines.

Uniform-sized nanoparticles (0.325 and 0.068 PDI) with mean diameters of 264.5 and 268.4 nm for blank and erlotinib-PLGA nanoparticles (nanodrugs-NDs) were formulated, respectively. The encapsulation efficiency of prepared nanoparticles was found to be 90.1%. 36% of erlotinib was released from PLGA nanoparticles within 24 h, and the maximum sustained release was 43% at 72 h. The metabolomic and cytotoxic effects of ND were evaluated.

The Bax/Bcl-2 ratio was the lowest in the nanodrug group at 72 h, showing increased apoptosis, indicating that the most effective drug formulation is the combined nanoparticle at 72 h. The metabolomic studies revealed changing amino acids, antioxidant molecules, and carbohydrate profiles. The most significant changes were obtained in pathways related to the synthesis of p-glycoprotein, which is the principal protein for drug efflux and causes drug resistance. The lowest levels of amino acids and polyamines like serine, threonine, spermine, and spermidine were obtained at 72 h with erlotinib encapsulated in poly(lactide-co-glycolide) (PLGA) nanoparticles, showing that the drug resistance may in part be overcome with this nanoparticles.

The encapsulation of erlotinib with PLGA showed effects and influenced critical metabolic pathways, especially pointing out the need to lower drug resistance and signifying it's potential use as an effective treatment strategy for NSCLC.

The tumour microenvironment (TME) presents a distinctive set of challenges and opportunities in the context of targeted cancer therapies, offering potential avenues for reducing non-specific cell death and side effects on normal cells. By combining chemodynamic therapy, starvation therapy, and photothermal therapy, our approach aims to activate drug release and generate reactive oxygen species within the TME. Specifically, we developed a fucoidan-chitosan (F/CS) nanocarrier loaded with 3,3',5,5'-tetramethylbenzidine (T), Prussian blue (P), and glucose oxidase (GOx) (F/CS@TPGOx). It has been reported that fucoidan and chitosan target P-selectin and the glucose-rich microenvironment of pathological cancer. Furthermore, F/CS@TPGOx at a concentration of 4 µg/mL was observed to reduce cancer cell viability to less than 20 % following a four-hour incubation period. This indicates that fucoidan, the carrier, exhibits anticancer activity that is more pronounced than that observed in conventional anticancer nanocarriers. The findings demonstrated the efficacy of F/CS@TPGOx in cancer cell death in both in vitro and in vivo settings. This suggests F/CS@TPGOx as a promising material for targeted cancer therapy with the potential to be used in clinical biomedicine as a therapeutic platform with high efficacy and minimal side effects.

Piglets with different weaning body weights exhibit varying growth performance. This study explores the relationship between their plasma metabolites and gut microbiota to reveal differences in metabolic regulation and microbial composition.

Plasma and colon content samples from piglets of different weaning weights were collected. Untargeted metabolomics, 16S rRNA gene sequencing, multivariate statistics, and bioinformatics were used to identify and compare metabolites. Six key findings emerged. First, 23 differential metabolites were found, with three upregulated in high-weight piglets and 20 downregulated in low-weight piglets. A total of 15 were lipids or lipid-like molecules. Second, metabolic pathway enrichment analysis indicated that the sphingolipid signaling pathway, HIF-1 signaling pathway, sphingolipid metabolism pathway, ascorbate and aldarate metabolism pathway, and glycine, serine, and threonine metabolism pathway were the most significantly affected pathways in the plasma of piglets with different weaning body weights. Third, alpha diversity was lower in low-weight weaned piglets. Fourth, Lactobacillus was 23.16% in high-weight piglets, higher than 19.62% in low-weight ones. Fifth, linear discriminant analysis effect size (LEfSe) analysis showed that Faecalibacterium is a biomarker for low-body-weight piglets and Oscillospira is a biomarker for high-body-weight piglets. Finally, Spearman correlation analysis indicated that Lactobacillus, Prevotella, Ruminococcus, and Oscillospira were negatively correlated with differential metabolites in plasma.

The plasma metabolites and colon microbiota differed between piglets of different body weights. Lipid-related plasma metabolites contributed to weight variation, being lower in heavier piglets. The colonic microbiota, especially Oscillospira and Roseburia, exhibited strong correlations with these metabolites. © 2025 Society of Chemical Industry.

The aberrant metabolic reprogramming endows TNBC cells with sufficient ATP and lactate required for survival and metastasis. Hence, the intervention of the metabolic network represents a promising avenue to alleviate the Warburg effect in TNBC cells to impair their invasive and metastatic potential. Multitudinous in-silico analysis identified Enolase1 (ENO1) and the surface transporter protein, GLUT4 to be the potential targets for the abrogation of the metabolic network. The expression profiles of ENO1 and GLUT4 genes showed anomalous expression in various cancers, including breast cancer. Subsequently, the functional and physiological interactions of the target proteins were analyzed from the protein-protein interaction network. The pathway enrichment analysis identified the prime cancer signaling pathways in which these proteins are involved. Further, docking results bestowed Silibinin as the concurrent inhibitor of ENO1 and GLUT4. Moreover, the stable interaction of Silibinin with both proteins deciphered the binding free energies values of -48.86 and -104.31 KJ/mol from MMPBSA analysis and MD simulation, respectively. Furthermore, the cell viability, ROS assay, and live-dead imaging underscored the pronounced cytotoxicity of Silibinin, illuminating its capacity to incur apoptosis within TNBC cells. Additionally, glycolysis assay and gene expression analysis demonstrated the silibinin-mediated inhibition of the glycolysis pathway. Eventually, a lipidomic reprogramming towards fatty acid metabolism was established from the elevated lipid droplet accumulation, exogenous fatty acid uptake and de-novo lipogenesis. Nevertheless, repression of EMT and Wnt pathway progression by Silibinin was perceived from the gene expression studies. Overall, the current study highlights the tweaking of intricate signaling crosstalk between glycolysis and the Wnt pathway in TNBC cells through inhibiting ENO1 and GLUT4.

Manipulation of the biochemical composition of the tumor microenvironment (TME) is a thriving research area in cancer treatment. Adenosine triphosphate (ATP), a key biochemical component, serves as an energy source for cancer cell proliferation. Notably, ATP can also act as a potent signal transducer to prime anti-tumor immune responses. There is increasing attention given to both the tumor-promoting and tumor-inhibiting roles of ATP in the context of possible new treatments for cancer. ATP levels in the TME are known to be significantly greater than in non-tumor tissues. This disparity presents an opportunity to exploit the ATP response for the delivery of anti-tumor drugs and tumor diagnosis. In this article, we provide a comprehensive overview of the existing strategies and mechanisms for ATP-based therapy and cancer diagnosis. We also discuss the current challenges in the field and propose potential areas for future research, to provide researchers with insights to further investigate the potential of ATP in cancer theranostics.

Metastasis is the primary cause of cancer mortality. It is responsible for 90% of all cancer-related deaths. Intercellular communication is a crucial feature underlying cancer metastasis and progression. Cancerous tumors secrete membrane-derived small extracellular vesicles (30-150 nm) into their extracellular milieu. These tiny organelles, known as exosomes, facilitate intercellular communication by transferring bioactive molecules. These exosomes harbor different cargos, such as proteins, nucleic acids, and lipids, that mediate multifaceted functions in various oncogenic processes. Of note, the amount of lipids in exosomes is multifold higher than that of other cargos. Most studies have investigated the role of exosomes' protein and nucleic acid content in various oncogenic processes, while the role of lipid cargo in cancer pathophysiology remains largely obscure.

We conducted an extensive literature review on the role of exosomes and lipids in cancer progression, specifically addressing the topic of exosomal lipids and their involvement in cancer metastasis and progression.

This review aims to shed light on the lipid contents of exosomes in cancer metastasis. In this context, the role of exosomal lipids in signaling pathways, immunomodulation, and energy production for cancer cell survival provides insights into overcoming cancer progression and metastasis.

Glucose transporters are essential carrier proteins that function on the phospholipid bilayer to facilitate glucose diffusion across cell membranes. The transporters play many physiological and pathological roles in addition to absorption and metabolism of fructose in food and the pathogenesis of gastrointestinal diseases. These carrier proteins play an important role in diseases of the nervous system, cardiovascular system, digestive system, and urinary system. These essential transporters have been extensively studied as potential therapeutic targets for cancers such as pancreatic, prostate, and hepatocellular carcinoma, which serve as diagnostic and prognostic indicators. The method uses position-specific scoring metrics (PSSM) with multiple-scanning windows-based convolutional neural networks to classify glucose transport proteins based on their functional significance and crucial role in therapy. Convolutional neural networks with multiple window scanning are employed to capture biologically meaningful, significant, and meaningful features from PSSM evolutionary profiles. Our proposed Method obtained Matthews correlation coefficients (MCC) of 0.99, Accuracy (AC) of 99.46, for Glucose facilitative transporters (GLUT), 0.99, 99.46, for Sodium Coupled glucose transporters (SGLT), and 0.92, and 97.3 for Sugars will eventually be exported transporters (SWEET) respectively. This study shows significantly higher performance than our previous study, which could be used to accurately classify novel glucose transporters.

Breast cancer is a widely prevalent and devastating morbidity that affects millions of women around the world. Conventional treatment options for breast cancer include surgery, chemotherapy, and radiotherapy. However, these therapies can frequently have adverse side effects and may not be effective for all patients. In recent years, there has been an increasing interest in the development of targeted therapies for breast cancer. Glut-1, a key glucose transporter that is often overexpressed in breast cancer cells, is a potential candidate for targeted therapies. Glut-1 is crucial for basal glucose transport into cancer cells and is necessary for their rapid growth and survival. Several Glut-1 inhibitors - both natural and synthetic small molecules - have been identified and used as anticancer agents. In this chapter, we summarize the different approaches of Glut-1 inhibition in breast cancer and the mode of inhibition used by various Glut-1 inhibitors. Further understanding of the mechanisms underlying the efficacy of Glut-1 inhibitors in breast cancer treatment may provide crucial insights that can lead to the advancement of current treatment strategies. The functional inhibition of Glut-1 by specific Glut-1 inhibitors is being explored as a potential treatment modality for breast cancer. This approach holds great promise for improving the therapeutic efficacy of breast cancer treatment and minimizing the side effects associated with conventional therapies.

Glucose transporters (GLUTs) play vital roles in cellular metabolism. Understanding their evolutionary dynamics in birds is essential for elucidating avian physiology and adaptation. However, the choice of gene detection method in gene family analysis may affect the conclusion. Here, we present a comprehensive investigation of methodologies and GLUT gene loss events in avian lineages, focusing on the loss of GLUT4 and GLUT8. To illustrate the effects of these methods, we first employed BUSCO-based homolog identification, calculated pairwise evolutionary distances between different species, and performed separate blastn and blastp searches to identify homologs in two groups of animals. Our analyses revealed a significant decline in blastn accuracy with increasing evolutionary distance, represented by relative divergence times. Through a more robust blastp-based gene detection pipeline, we provide evidence for the loss of GLUT genes in birds based on 58 vertebrate genomes, including 47 bird species. Our results support the reported early loss of GLUT4 in Aves. We also newly emphasize the absence of GLUT8 in passerines, potentially due to adaptation to high-sugar diets in their ancestors. These findings enhance our knowledge of avian metabolism and the evolution of GLUT genes.

Metabolic reprogramming and altered cellular energetics have been recently established as an important cancer hallmark. The modulation of glucose metabolism is one of the important characteristic features of metabolic reprogramming in cancer. It contributes to oncogenic progression by supporting the increased biosynthetic and bio-energetic demands of tumor cells. This oncogenic transformation consequently results in elevated expression of glucose transporters in these cells. Moreover, various cancers exhibit abnormal transporter expression patterns compared to normal tissues. Recent investigations have underlined the significance of glucose transporters in regulating cancer cell survival, proliferation, and metastasis. Abnormal regulation of these transporters, which exhibit varying affinities for hexoses, could enable cancer cells to efficiently manage their energy supply, offering a crucial edge for proliferation. Exploiting the upregulated expression of glucose transporters, GLUTs, and Sodium Linked Glucose Transporters (SGLTs), could serve as a novel therapeutic intervention for anti-cancer drug discovery as well as provide a unique targeting approach for drug delivery to specific tumor tissues. This review aims to discussthe previous and emerging research on the expression of various types of glucose transporters in tumor tissues, the role of glucose transport inhibitors as a cancer therapy intervention as well as emerging GLUT/SGLT-mediated drug delivery strategies that can be therapeutically employed to target various cancers.

The mechanistic target of rapamycin kinase (MTOR) is pivotal for cell growth, metabolism, and survival. It functions through two distinct complexes, mechanistic TORC1 and mechanistic TORC2 (mTORC1 and mTORC2). These complexes function in the development and progression of cancer by regulating different cellular processes, such as protein synthesis, lipid metabolism, and glucose homeostasis. The mTORC1 complex senses nutrients and initiates proliferative signals, and mTORC2 is crucial for cell survival and cytoskeletal rearrangements. mTORC1 and mTORC2 have therefore emerged as potential targets for cancer treatment. Several mTOR inhibitors, including rapamycin and its analogs (rapalogs), primarily target mTORC1 and are effective for specific cancer types. However, these inhibitors often lead to resistance and limited long-term advantages due to the activation of survival pathways through feedback mechanisms. Researchers have created next-generation inhibitors targeting mTORC1 and mTORC2 and dual PI3K/mTOR inhibitors to address these difficulties. These inhibitors demonstrate enhanced anti-tumor effects by simultaneously disrupting multiple signaling pathways and show promise for improved and long-lasting therapies. However, development of resistance and adverse side effects remain a significant obstacle. Recent additions known as RapaLinks have emerged as a boon to counter drug-resistant cancer cells, as they are more potent and provide a more comprehensive blockade of mTOR signaling pathways. This Review combines current research findings and clinical insights to enhance our understanding of the crucial role of mTOR signaling in cancer biology and highlights the evolution of mTOR inhibitors as promising therapeutic approaches.

Boronated carbohydrate derivatives have good potential for targeting malignant cells in Boron Neutron Capture Therapy (BNCT) due to their preferential glucose uptake. In particular, with the introduction of the ammonium trifluoroborate moiety, boronated sugars can function as both BNCT agents and Positron Emission Tomography (PET) tracers. Their 18F radiolabeling allows real-time tracking of biodistribution. This study evaluates the chemical, metabolic, and plasma stability of ammonium trifluoroborates for pharmaceutical purposes using LC-HRMS, presenting stability data under various conditions -acidic, basic, pseudophysiological, and oxidative- and highlighting degradation products and mechanisms. The data are supported by 1H NMR and 19F NMR. Metabolic and plasma stabilities, along with preliminary toxicological data (MTT assays), are also provided to better predict the clinical applicability of these compounds.

Similar to other malignancies, immune dysregulation is a key feature of acute myeloid leukemia (AML), manifesting as suppressed anti-leukemia immune cells, immune evasion by leukemia blasts, and disease progression. Various immunosuppressive factors within the AML microenvironment contribute to the weakening of host immune responses and the efficacy of cellular immunotherapy. To address these challenges, strategies targeting immunosuppressive elements within the AML microenvironment aim to bolster host or adoptive immune effector cells, ultimately enhancing leukemia treatment. Additionally, the off-target effects of certain targeted drugs (venetoclax, sorafenib, ivosidenib, etc.) may also positively impact anti-AML immunity and immunotherapy. This review provides an overview of the immunosuppressive factors present in AML microenvironment and the strategies developed to rescue immune cells from immunosuppression. We also outline how targeted agents can alter the immune landscape in AML patients, and discuss the potential of targeted drugs to benefit host anti-leukemia immunity and immunotherapy for AML.

In the present study, a detailed analysis of the effect of a substitution at the C4 position of the quinoline ring by styryl or furanylvinyl substituents on the structure-antitumour activity relationship was conducted. After analysing a library of derivatives from the styrylquinoline and furanylvinylquinoline groups, we selected the most active (IC50 below 100 nM) derivative 13, which contained the strongly electron-withdrawing nitro group in the furan substituent. The mechanism of action of this compound was studied on cell lines that differed in their p53 protein status. For this derivative, both cell cycle arrest (in G2/M phase in both HCT 116 cell lines and S phase for U-251 cell line) and the induction of apoptosis (up to 66% for U-251 cell line) were revealed. These studies were then confirmed by other methods at the gene and protein levels. Interestingly, we observed differences in the mechanism of action depending on the presence and mutation of the p53 protein, thus confirming its key role in cellular processes. Incubation with derivative 13 resulted in the induction of oxidative stress and triggered a cascade of cellular defence proteins that failed in the face of such an active compound. In addition, the results showed an inhibition of the GLUT-1 glucose transporter, which is extremely important in the context of anti-cancer activity.

Recent discoveries demonstrated the skeleton's role as an endocrine organ regulating whole-body glucose homeostasis. Glucose metabolism is critical for rapid cell proliferation and tumour growth through increasing glucose uptake and fermentation of glucose to lactate despite being in an aerobic environment. This hypothesis paper discusses emerging evidence on how bones can regulate whole-body glucose homeostasis with potential to impact on tumour growth and proliferation. Moreover, it proposes a clinical link between bone glucose metabolism and prognosis of cancer based on recent clinical trial data. Targeting metabolic pathways related with classic glucose metabolism and also bone metabolism, novel methods of cancer therapy and treatment could be developed. This paper objective is to highlight the need for future research on this altered metabolism with potential to change future management of cancer patients.

Mitochondria, traditionally known as cellular powerhouses, now emerge as critical signaling centers influencing cancer progression and drug resistance. The review highlights the role that apoptotic signaling, DNA mutations, mitochondrial dynamics and metabolism play in the development of resistance mechanisms and the advancement of cancer. Targeted approaches are discussed, with an emphasis on managing mitophagy, fusion, and fission of the mitochondria to make resistant cancer cells more susceptible to traditional treatments. Additionally, metabolic reprogramming can be used to effectively target metabolic enzymes such GLUT1, HKII, PDK, and PKM2 in order to avoid resistance mechanisms. Although there are potential possibilities for therapy, the complex structure of mitochondria and their subtle role in tumor development hamper clinical translation. Novel targeted medicines are put forth, providing fresh insights on combating drug resistance in cancer. The study also emphasizes the significance of glutamine metabolism, mitochondrial respiratory complexes, and apoptotic pathways as potential targets to improve treatment effectiveness against drug-resistant cancers. Combining complementary and nanoparticle-based techniques to target mitochondria has demonstrated encouraging results in the treatment of cancer, opening doors to reduce resistance and enable individualized treatment plans catered to the unique characteristics of each patient. Suggesting innovative approaches such as drug repositioning and mitochondrial drug delivery to enhance the efficacy of mitochondria-targeting therapies, presenting a pathway for advancements in cancer treatment. This thorough investigation is a major step forward in the treatment of cancer and has the potential to influence clinical practice and enhance patient outcomes.

While traditional high-dose chemotherapy can effectively prolong the overall survival of acute myeloid leukemia (AML) patients and contribute to better prognostic outcomes, the advent of chemoresistance is a persistent challenge to effective AML management in the clinic. The therapeutic resistance is thought to emerge owing to the heterogeneous and adaptable nature of tumor cells when exposed to exogenous stimuli. Recent studies have focused on exploring metabolic changes that may afford novel opportunities to treat AML, with a particular focus on glycolytic metabolism. The Warburg effect, a hallmark of cancer, refers to metabolism of glucose through glycolysis under normoxic conditions, which contributes to the development of chemoresistance. Despite the key significance of this metabolic process in the context of malignant transformation, the underlying molecular mechanisms linking glycolysis to chemoresistance in AML remain incompletely understood. This review offers an overview of the current status of research focused on the relationship between glycolytic metabolism and AML resistance to chemotherapy, with a particular focus on the contributions of glucose transporters, key glycolytic enzymes, signaling pathways, non-coding RNAs, and the tumor microenvironment to this relationship. Together, this article will provide a foundation for the selection of novel therapeutic targets and the formulation of new approaches to treating AML.

Metabolic reprogramming is recognized as a hallmark of cancer, enabling cancer cells to acquire essential biomolecules for cell growth, often characterized by upregulated glycolysis and/or fatty acid synthesis-related genes. The transcription factor forkhead box M1 (FOXM1) has been implicated in various cancers, contributing significantly to their development, including colorectal cancer (CRC), a major global health concern. Despite FOXM1's established role in cancer, its specific involvement in the Warburg effect and fatty acid biosynthesis in CRC remains unclear. We analyzed The Cancer Genome Atlas (TCGA) Colonic Adenocarcinoma and Rectal Adenocarcinoma (COADREAD) datasets to derive the correlation of the expression levels between FOXM1 and multiple genes and the survival prognosis based on FOXM1 expression. Using two human CRC cell lines, HT29 and HCT116, we conducted RNAi or plasmid transfection procedures, followed by a series of assays, including RNA extraction, quantitative real-time polymerase chain reaction, Western blot analysis, cell metabolic assay, glucose uptake assay, Oil Red O staining, cell viability assay, and immunofluorescence analysis. Higher expression levels of FOXM1 correlated with a poorer survival prognosis, and the expression of FOXM1 was positively correlated with glycolysis-related genes SLC2A1 and LDHA, de novo lipogenesis-related genes ACACA and FASN, and MYC. FOXM1 appeared to modulate AKT/mammalian target of rapamycin (mTOR) signaling, the expression of c-Myc, proteins related to glycolysis and fatty acid biosynthesis, and glucose uptake, as well as extracellular acidification rate in HT29 and HCT116 cells. In summary, FOXM1 plays a regulatory role in glycolysis, fatty acid biosynthesis, and cellular energy consumption, thereby influencing CRC cell growth and patient prognosis.NEW & NOTEWORTHY Transcription factor forkhead box M1 (FOXM1) regulates glycolysis, fatty acid biosynthesis, and cellular energy consumption, which, together, controls cell growth and patient prognosis in colorectal cancer (CRC).

Acute Myeloid Leukemia (AML) is a fast-developing invading cancer that impacts the blood and bone marrow, marked by the rapid proliferation of abnormal white blood cells. Chemotherapeutic agents, a primary treatment for AML, encounter clinical limitations such as poor solubility and low bioavailability. Previous studies have highlighted antibiotics as effective in inducing cancer cell death and potentially preventing metastasis. Besides, insulin is known to activate the PI3K/Akt pathway, often disrupted in cancers, leading to enhanced cell survival and resistance to apoptosis. In light of the above-mentioned points, we examined the anti-cancer impact of antibiotics Ciprofloxacin (CP) and Salinomycin (SAL) and their combination on KG1-a cells in the presence and absence of insulin.

This was accomplished by exposing KG1-a cells to different doses of CP and SAL alone, in combination, and with or without insulin for 24-72 h. Cell viability was evaluated using the MTT assay. Besides, apoptotic effects were examined using Hoechst staining and Annexin-V/PI flow cytometry. The expression levels of Bax, p53, BIRC5, Akt, PTEN, and FOXO1 were analyzed through Real-Time PCR.

CP and SAL demonstrated cytotoxic and notable pro-apoptotic impact on KG1-a cells by upregulating Bax and p53 and downregulating BIRC5, leading to G0/G1 cell cycle arrest and prevention of the PI3K-Akt signaling pathway. Our findings demonstrated that combination of CP and SAL promote apoptosis in the KG1-a cell line by down-regulating BIRC5 and Akt, as well as up-regulating Bax, p53, PTEN, and FOXO1. Additionally, the findings strongly indicated that insulin effectively mitigates apoptosis by enhancing Akt expression and reducing FOXO1 and PTEN gene expression in the cells treated with CP and SAL.

Our findings showed that the combined treatment of CP and SAL exhibit a strong anti-cancer effect on leukemia KG1-a cells. Moreover, it was discovered that the PI3K-Akt signaling can be a promising target in leukemia treatment particularly in hyperinsulinemia condition.

Iron is often accumulated in the liver during pathological conditions such as cirrhosis and cancer. Elevated expression of glucose transporters GLUT1 and GLUT3 is associated with reduced overall survival in patients with hepatocellular carcinoma. However, it is not known whether iron can regulate glucose transporters and contribute to tumor proliferation. In the present study, we found that treatment of human liver cell line HepG2 with ferric ammonium citrate (FAC) resulted in a significant upregulation of GLUT3 mRNA and protein in a dose-dependent manner. Similarly, iron accumulation in mice fed with high dietary iron as well as in mice injected intraperitoneally with iron dextran enhanced the GLUT3 expression drastically in the liver. We demonstrated that iron-induced hepatic GLUT3 upregulation is mediated by the LKB1/AMPK/CREB1 pathway, and this activation was reversed when treated with iron chelator deferiprone. In addition, inhibition of GLUT3 using siRNA prevented iron-mediated increase in the expression of cell cycle markers and cellular hyperproliferation. Furthermore, exogenous sodium beta-hydroxybutyrate treatment prevented iron-mediated hepatic GLUT3 activation both in vitro and in vivo. Together, these results underscore the importance of iron, AMPK, CREB1 and GLUT3 pathways in cell proliferation and highlight the therapeutic potential of sodium beta-hydroxybutyrate in hepatocellular carcinoma with high GLUT3 expression.

A series of C2-functionalied Pt (IV) glycoconjugates based on glucosamine have been synthesised, characterised and tested as anticancer agents on a series of different 2D and 3D cancer cell lines. The carbohydrate will act as a targeted delivery system to improve the selectivity, exploiting the Warburg Effect and the GLUTs receptors that are overexpressed in most of the cancer cells. The hydroxyl at C2 of the carbohydrates does not participate in hydrogen bonding with the GLUTs receptors, making C2 an attractive position for drug conjugation as seen in literature. In this study, we use the amino functionality at the C2 position in glucosamine and Copper-catalysed Azide-Alkyne Cycloaddition "click" (CuAAC) reaction to connect the prodrug Pt (IV) scaffold to the carbohydrate. We have investigated complexes with different linker lengths, as well as acetyl protected and free derivatives. To the best of our knowledge, this study represents the first series of Pt (IV) glucosamine-conjugates functionalised at C2.

Higher demand for nutrients including glucose is characteristic of cancer. "Starving cancer" has been pursued to curb tumor progression. An intriguing regime is to inhibit glucose transporter GLUT1 in cancer cells. In addition, during cancer progression, cancer cells may suffer from insufficient glucose supply. Yet, cancer cells can somehow tolerate glucose starvation. Uncovering the underlying mechanisms shall shed insight into cancer progression and benefit cancer therapy. TFE3 is a transcription factor known to activate autophagic genes. Physiological TFE3 activity is regulated by phosphorylation-triggered translocation responsive to nutrient status. We recently reported TFE3 constitutively localizes to the cell nucleus and promotes cell proliferation in kidney cancer even under nutrient replete condition. It remains unclear whether and how TFE3 responds to glucose starvation. In this study, we show TFE3 promotes kidney cancer cell resistance to glucose starvation by exposing cells to physiologically relevant glucose concentration. We find glucose starvation triggers TFE3 protein stabilization through increasing its O-GlcNAcylation. Furthermore, through an unbiased functional genomic study, we identify SLC36A1, a lysosomal amino acid transporter, as a TFE3 target gene sensitive to TFE3 protein level. We find SLC36A1 is overexpressed in kidney cancer, which promotes mTOR activity and kidney cancer cell proliferation. Importantly, SLC36A1 level is induced by glucose starvation through TFE3, which enhances cellular resistance to glucose starvation. Suppressing TFE3 or SLC36A1 significantly increases cellular sensitivity to GLUT1 inhibitor in kidney cancer cells. Collectively, we uncover a functional TFE3-SLC36A1 axis that responds to glucose starvation and enhances starvation tolerance in kidney cancer.

Cancer is one of the major causes of death worldwide, even the second foremost cause related to non-communicable diseases. Cancer cells typically possess several cellular and biological processes including, persistence, propagation, differentiation, cellular death, and expression of cellular-type specific functions. The molecular picture of carcinogenesis and progression is unwinding, and it appears to be a tangled combination of processes occurring within and between cancer cells and their surrounding tissue matrix. Polyphenols are plant secondary metabolites abundant in fruits, vegetables, cereals, and other natural plant sources. Natural polyphenols have implicated potential anticancer activity by various mechanisms involved in their antitumor action, including modulation of signaling pathways majorly related to cellular proliferation, differentiation, relocation, angiogenesis, metastatic processes, and cell death. The applications of polyphenols have been limited due to the hydrophobic nature and lower oral bioavailability that could be possibly overcome through encapsulating them into nanocarrier-mediated delivery systems, leading to improved anticancer activity. Nanoemulsions (NEs) possess diverse feasible properties, including greater surface area, modifiable surficial charge, higher half-life, site-specific targeting, and formulation imaging capability necessary to create a practical therapeutic impact, and have drawn increased attention in cancer therapy research. This review has summarized and discussed the basic concepts, classification, delivery approaches, and anticancer mechanism of various polyphenols and polyphenols-encapsulated nanoemulsions with improved cancer therapy.

Lactate dehydrogenase A (LDHA) serves as a key regulator of the Warburg Effect by catalyzing the conversion of pyruvate to lactate in the final step of glycolysis. Both the expression level and enzyme activity of LDHA are upregulated in cancers, however, the underlying mechanism remains incompletely understood. Here, we show that LDHA is post-translationally palmitoylated by ZDHHC9 at cysteine 163, which promotes its enzyme activity, lactate production, and reduces reactive oxygen species (ROS) generation. Replacement of endogenous LDHA with a palmitoylation-deficient mutant leads to reduced pancreatic cancer cell proliferation, increased T-cell infiltration, and limited tumor growth; it also affects pancreatic cancer cell response to chemotherapy. Moreover, LDHA palmitoylation is upregulated in gemcitabine resistant pancreatic cancer cells. Clinically, ZDHHC9 is upregulated in pancreatic cancer and correlated with poor prognoses for patients. Overall, our findings identify ZDHHC9-mediated palmitoylation as a positive regulator of LDHA, with potentially significant implications for cancer etiology and targeted therapy for pancreatic cancer.

Adipose tissue is a complex organ that is increasingly being recognised as the largest endocrine organ in the body. Adipocytes among multiple cell types of adipose tissue can secrete a variety of adipokines, which are involved in signalling pathways and these can be changed by obesity and cancer. There are proposed mechanisms to link obesity/adiposity to cancer development including adipocytokine dysregulation. Among these adipokines, leptin acts through multiple pathways including the STAT3, MAPK, and PI3K pathways involved in cell growth. Adiponectin has the opposite action from leptin in tumour growth partly because of increased apoptotic responses of p53 and Bax. Visfatin increases cancer cell proliferation through ERK1/2, PI3K/AKT, and p38 which are stimulated by proinflammatory cytokines. Omentin through the PI3K/Akt-Nos pathway is involved in cancer-tumour development. Apelin might be involved through angiogenesis in tumour progressions. PAI-1 via its anti-fibrinolytic activity on cell adhesion and uPA/uPAR activity influence cancer cell growth.

Pancreatic carcinoma is a highly aggressive tumor that usually presents when it has already metastasized. Therapeutic options for cure remain scarce and rely on combination chemotherapy with limited sustainability. Diabetes is considered an important risk factor for the development of pancreatic cancer due to the production of proinflammatory cytokines, which result in increased cell proliferation. More than half of patients diagnosed with pancreatic cancer eventually develop diabetes due to the destruction of insulin-producing cells. The interlinkage of both diseases might identify a possible preventative strategy for reducing the incidence of pancreatic carcinoma. This study reviewed the recent literature on the association between pancreatic cancer risk and SGLT2 inhibitors, GLP-1 RA, DPP-4 inhibitors, and biguanides. There are mixed data regarding the relationship between GLP-1 RA and DPP-4 inhibitors and pancreatic cancer, with some trials suggesting that they might increase the risk. In contrast, studies have mostly revealed that SGLT2 inhibitors have an antiproliferative effect on various tumors, such as liver, pancreatic, prostate, bowel, lung, and breast carcinoma, which might be due to their mechanism of blockage of reabsorption of glucose by cells, lowering the amount of available glucose for the growth of tumor cells. Metformin, the first-line agent for diabetes, has also been shown to be associated with decreasing pancreatic cancer risk and improving prognosis in those who already have the disease. Dedicated trials are needed to further delineate the association of antidiabetic drugs with the risk of pancreatic cancer in the general population, as previous studies have mostly focused on diabetic patients.

The first definitive hematopoietic progenitors emerge through the process of endothelial-to-hematopoietic transition in vertebrate embryos. With molecular regulators for this process worked out, the role of metabolic pathways used remains unclear. Here, we performed nano-LC-MS/MS-based proteomic analysis and predicted a metabolic switch from a glycolytic to oxidative state upon hematopoietic transition. Mitochondrial activity, glucose uptake, and glycolytic flux analysis supported this hypothesis. Systemic inhibition of lactate dehydrogenase A (LDHA) increased oxygen consumption rate in the hemato-endothelial system and inhibited the emergence of intra-aortic hematopoietic clusters. These findings were corroborated using Tie2-Cre-mediated deletion of Ldha that showed similar effects on hematopoietic emergence. Conversely, stabilization of HIF-1α via inhibition of oxygen-sensing pathway led to decreased oxidative flux and promoted hematopoietic emergence in mid-gestation embryos. Thus, cell-intrinsic regulation of metabolic state overrides oxygenated microenvironment in the aorta to promote a glycolytic metabolic state that is crucial for hematopoietic emergence in mammalian embryos.

Protein S-palmitoylation is a reversible post-translational lipid modification that involves the addition of a 16-carbon palmitoyl group to a protein cysteine residue via a thioester linkage. This modification plays a crucial role in the regulation protein localization, accumulation, secretion, stability, and function. Dysregulation of protein S-palmitoylation can disrupt cellular pathways and contribute to the development of various diseases, particularly cancers. Aberrant S-palmitoylation has been extensively studied and proven to be involved in tumor initiation and growth, metastasis, and apoptosis. In addition, emerging evidence suggests that protein S-palmitoylation may also have a potential role in immune modulation. Therefore, a comprehensive understanding of the regulatory mechanisms of S-palmitoylation in tumor cells and the tumor immune microenvironment is essential to improve our understanding of this process. In this review, we summarize the recent progress of S-palmitoylation in tumors and the tumor immune microenvironment, focusing on the S-palmitoylation modification of various proteins. Furthermore, we propose new ideas for immunotherapeutic strategies through S-palmitoylation intervention.

Glucose is the major source of chemical energy for cell functions in living organisms. The aim of this mini-review is to provide a clearer and simpler picture of the fundamentals of glucose transporters as well as the relationship of these transporters to Alzheimer's disease. This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Electronic databases (PubMed and ScienceDirect) were used to search for relevant studies mainly published during the period 2018-2023. This mini-review covers the two main types of glucose transporters, facilitated glucose transporters (GLUTs) and sodium-glucose linked transporters (SGLTs). The main difference between these two types is that the first type works through passive transport across the glucose concentration gradient. The second type works through active co-transportation to transport glucose against its chemical gradient. Fluctuation in glucose transporters translates into a disturbance of normal functioning, such as Alzheimer's disease, which may be caused by a significant downregulation of GLUTs most closely associated with insulin resistance in the brain. The first sign of Alzheimer's is a lack of GLUT4 translocation. The second sign is tau hyperphosphorylation, which is caused by GLUT1 and 3 being strongly upregulated. The current study focuses on the use of glucose transporters in treating diseases because of their proven therapeutic potential. Despite this, studies remain insufficient and inconclusive due to the complex and intertwined nature of glucose transport processes. This study recommends further understanding of the mechanisms related to these vectors for promising future therapies.

MicroRNAs (miRNAs) are well-established post-translational non-coding RNAs that play crucial roles in mRNA degradation and repression. Glucose transporter 1 (GLUT1) showed correlation along with various miRNA, specifically miRNA10a expression in lung cancers. The role of miRNA10a along with glucose upregulation leading to cancer proliferation in oral squamous cell carcinoma (OSCC) is unknown. This study aimed to investigate the expression levels of miRNA10a and GLUT1 in OSCC patients with diabetes.

miRNA10a and GLUT1 expression were estimated in OSCC, precancerous, and healthy tissues using quantitative reverse transcriptase polymerase chain reaction (RT-PCR). miRNA10a and GLUT1 expression levels were recorded as fold change. Further, a one-way analysis of variance (ANOVA) test was performed to find whether there is any difference in miRNA10a and GLUT1 expression between OSCC, precancerous, and healthy tissues.

The RT-PCR findings revealed an increased expression of miRNA10a and GLUT1 in OSCC compared to precancerous and healthy tissue. There is a positive correlation between miRNA10a and GLUT1 expression levels in both potentially malignant and control tissues, with a marked increase in cancerous tissue. This study demonstrated the significance of upregulated miRNA10a expression, indicating a direct correlation with OSCC proliferation via GLUT1 overexpression. Specifically, miRNA10a exhibited a fold change of 1.2±0.072 in potentially malignant tissue and 1.4±0.05 in cancer tissue, while GLUT1 exhibited a fold change of 1.25±0.092 in potentially malignant tissue and 0.092±0.08 in cancer tissue, respectively.

This research highlights the role of miRNA10a in cancer progression by facilitating proliferation through the regulation of GLUT1 in cancerous tissues, particularly in hyperglycemic conditions. This mechanism further contributes to increased glucose transport in cancer patients, which may potentially impede tumor prognosis. These findings underscore the potential significance of targeting miRNA10a and GLUT1 as therapeutic interventions in cancer management.

Ovarian cancer (OC) is one of the most prevalent malignancies in female reproductive organs, and its 5-year survival is below 45%. Despite the advances in surgical and chemotherapeutic options, OC treatment is still a challenge, and new anticancer agents are urgently needed. Drug repositioning has gained significant attention in drug discovery, representing a smart way to identify new clinical applications for drugs whose human safety and pharmacokinetics have already been established, with great time and cost savings in pharmaceutical development endeavors. This review offers an update on the most promising drugs repurposable for OC treatment and/or prevention.

Hypoxia can cause significant changes in the glucose metabolism of cancer cells that prefer aerobic glycolysis for energy production instead of the conventional oxidative phosphorylation mechanism. In this study, breast cancer cells (MCF-7) were exposed to glucose (0-5.5-15-55 mM), during specific incubation periods (3, 6, 12, or 24 hours) under normoxic and hypoxic conditions. The expression levels of hypoxia-inducible factor-1α (HIF-1α), glucose transporter-1 (GLUT-1), and glycolytic enzymes at varying glucose concentrations in cells were investigated in the different oxygen environments. It was determined that glycolytic enzymes [Hexokinase 2 (HK2), Pyruvate Kinase M2 (PKM2), Glucose-6-phosphate dehydrogenase (G6PD), Lactate Dehydrogenase A (LDHA), Glyceraldehyde-3-phosphate Dehydrogenase (GAPDH), and Phosphofructokinase M (PFKM)] increased at the transcriptional level, especially in the first hours. This increase indicates that major metabolic reprogramming in response to hypoxia probably occurs over a short period of time. The increase in G6PD gene expression under high glucose and hypoxia conditions suggests that the pentose phosphate pathway (PPP) is used by cancer cells to synthesize necessary precursors for the cell. The results of the study showed that there is a significant interaction between hypoxia and glycolytic metabolism in cancer cells. It is thought that metabolic pathways activated by hypoxia and related genes located in these pathways will contribute to the literature by offering the potential to be target molecules for therapeutic purposes.

Hepatocellular carcinoma (HCC) is a grievous tumor with an increasing incidence worldwide. Basic transcription factor 3 (BTF3) is discovered to regulate the expression of glucose transporter 1 (GLUT1), which benefits glycolysis, a momentous signature of tumors, through transactivation of the forkhead box M1 (FOXM1) expression. BTF3 is highly expressed in HCC. However, whether BTF3 promotes GLUT1 expression through FOXM1 to modulate glycolysis in HCC remains unclear. The expression profile of BTF3 were determined by online database, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot. The role and mechanism of BTF3 in the proliferation and glycolysis of HCC cells were examined by cell counting kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU) incorporation, XF96 Extracellular Flux analyzer, spectrophotometry and western blot analysis. In addition, the direct interaction between BTF3 and FOXM1 was verified by dual-luciferase reporter and co-immunoprecipitation assays. Moreover, the role of BTF3 was also explored in a xenografted mice model. The expression of BTF3 was increased in HCC cells and tumor tissues. Knockdown of BTF3 reduced the cell viability, Edu positive cells, extracellular acidification rate (ECAR), glucose consumption and lactate production in both Huh7 and HCCLM3 cells. The expressions of FOXM1 and GLUT1 were increased in HCC tissues, which were positively correlated with the BTF3 expression. Moreover, a direct interaction existed between BTF3 and FOXM1 in HCC cells. Downregulation of BTF3 decreased the relative protein levels of FOXM1 and GLUT1, which were rescued with overexpression of FOXM1 in both cells. More importantly, overexpression of FOXM1 restored the cell viability, ECAR, glucose consumption and lactate production in both Huh7 and HCCLM3 cells transfected with siBTF3#1. Furthermore, inhibition of BTF3 decreased tumor weight and volume, and the relative level of BTF3, FOXM1, GLUT1 and Ki-67 in tumor tissues from mice xenografted with Huh7 cells. BTF3 enhanced the cell proliferation and glycolysis through FOXM1/GLUT1 axis in HCC.

The aim of study was to investigate the correlation of GLUT3 upregulation and butyrate-mediated acquired chemoresistance.

A butyrate-resistant CRC cell model was established from parental (PT) HCT116 cells by gradually increasing the concentration of sodium butyrate (NaBu), followed by evaluation of resistance to butyrate and trichostatin A (TSA) by the MTT method. The expression of SLC2A3 gene and GLUT3 protein were assessed by semi-quantitative RT-PCR and western blotting, respectively. The correlation of GLUT3 and butyrate-induced acquired chemoresistance was investigated using SLC2A3 silencing.

Butyrate-resistant (BR) HCT116 cells were more tolerant to butyrate-induced cell death and also resist to 750 and 1000 nM TSA when compared with HCT116-PT cells (p <0.05). Long-term exposure to butyrate revealed that upregulation of the SLC2A3 gene was significantly increased by more than 20 fold (p < 0.01), and that of GLUT3 was elevated by approximately 2 fold (p < 0.05) in HCT116-BR cells. Silencing of the SLC2A3 gene increased the sensitivity of HCT116-BR cells to the effects of TSA.

Upregulation of GLUT3 is associated with resistance to butyrate and TSA. GLUT3 is a molecular target for the detection of chemoresistant CRC cells and thus a potential target for diagnostic strategies.

Targeting tumour metabolism through glucose transporters is an attractive approach. However, the role these transporters play through interaction with other signalling proteins is not yet defined. The glucose transporter SLC2A3 (GLUT3) is a member of the solute carrier transporter proteins. GLUT3 has a high affinity for D-glucose and regulates glucose uptake in the neurons, as well as other tissues. Herein, we show that GLUT3 is involved in the uptake of arsenite, and its level is regulated by peroxiredoxin 1 (PRDX1). In the absence of PRDX1, GLUT3 mRNA and protein expression levels are low, but they are increased upon arsenite treatment, correlating with an increased uptake of glucose. The downregulation of GLUT3 by siRNA or deletion of the gene by CRISPR cas-9 confers resistance to arsenite. Additionally, the overexpression of GLUT3 sensitises the cells to arsenite. We further show that GLUT3 interacts with PRDX1, and it forms nuclear foci, which are redistributed upon arsenite exposure, as revealed by immunofluorescence analysis. We propose that GLUT3 plays a role in mediating the uptake of arsenite into cells, and its homeostatic and redox states are tightly regulated by PRDX1. As such, GLUT3 and PRDX1 are likely to be novel targets for arsenite-based cancer therapy.

The sensitivity of [18F] fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) for detecting hepatocellular carcinoma (HCC) has not been clarified thoroughly. Our study seeks to explore the association between the Ki-67 index and FDG-avidity in HCC tumors using 18F-FDG PET/CT.

112 HCC lesions from 109 patients detected by 18F-FDG PET/CT were included retrospectively between August 2017 and May 2022, comprising 82 lesions in the training cohort and 30 in the validation cohort to simulate prospective studies. In the training cohort, lesions were stratified by a lesion-to-liver maximum standardized uptake value (SUVmax) ratio cut-off of 1.59. The relationships between lesion-to-liver SUVmax ratios and several clinical factors including tumor differentiation, alpha fetoprotein (AFP), carcinoembryonic antigen (CEA), hepatitis B virus (HBV) infection, Ki-67 index et al. were assessed. These findings were subsequently validated in the independent validation cohort.

In the training cohort, group A1 lesions demonstrated a higher Ki-67 index (%, 40.00 [30.00, 57.50] vs. 10.00 [5.00, 28.75], p<0.001) than group A0, the positive correlation between FDG-avidity and Ki-67 index was revealed by multivariate analysis, OR=1.040, 95% CI of OR [1.004-1.077], p=0.030. The calculated cut-off value was 17.5% using the receiver operating characteristic (ROC) curve, with an area under curve (AUC) of 0.834 and 95% CI [0.742-0.926], p<0.001. These findings were further validated in the independent validation cohort, with similar results (AUC=0.875, 95% CI [0.750-1.000], p<0.001).

In comparison to tumor differentiation, Ki-67 index demonstrates a stronger association with FDG-avidity in HCC tumors, and when the Ki-67 index exceeds 17.5%, 18F-FDG PET/CT might serve as a useful indicator for HCC.

Although the incidence of thyroid cancer is increasing year by year, most patients, especially those with differentiated thyroid cancer, can usually be cured with surgery, radioactive iodine, and thyroid-stimulating hormone suppression. However, treatment options for patients with poorly differentiated thyroid cancers or radioiodine-refractory thyroid cancer have historically been limited. Altered energy metabolism is one of the hallmarks of cancer and a well-documented feature in thyroid cancer. In a hypoxic environment with extreme nutrient deficiencies resulting from uncontrolled growth, thyroid cancer cells utilize "metabolic reprogramming" to satisfy their energy demand and support malignant behaviors such as metastasis. This review summarizes past and recent advances in our understanding of the reprogramming of glucose metabolism in thyroid cancer cells, which we expect will yield new therapeutic approaches for patients with special pathological types of thyroid cancer by targeting reprogrammed glucose metabolism.

Brain metastases (BM) cause relevant morbidity and mortality in cancer patients. The presence of cerebrovascular diseases can alter the tumor microenvironment, cellular proliferation and treatment resistance. However, it is largely unknown if the presence of distinct cerebrovascular risk factors may alter the prognosis of patients with BM.

Patients admitted for the radiotherapy of BM at a large tertiary cancer center were included. Patient and survival data, including cerebrovascular risk factors (diabetes mellitus (DM), smoking, arterial hypertension, peripheral arterial occlusive disease, hypercholesterolemia and smoking) were recorded.

203 patients were included. Patients with DM (n = 39) had significantly shorter overall survival (OS) (HR 1.75 (1.20-2.56), p = 0.003, log-rank). Other vascular comorbidities were not associated with differences in OS. DM remained prognostically significant in the multivariate Cox regression including established prognostic factors (HR 1.92 (1.20-3.06), p = 0.006). Furthermore, subgroup analyses revealed a prognostic role of DM in patients with non-small cell lung cancer, both in univariate (HR 1.68 (0.97-2.93), p = 0.066) and multivariate analysis (HR 2.73 (1.33-5.63), p = 0.006), and a trend in melanoma patients.

DM is associated with reduced survival in patients with BM. Further research is necessary to better understand the molecular mechanisms and therapeutic implications of this important interaction.

Metabolic reprogramming is known as an emerging mechanism of chemotherapy resistance, but the metabolic signatures of pancreatic ductal adenocarcinomas (PDACs) remain unclear. Here, we characterize the metabolomic profile of PDAC organoids and classify them into glucomet-PDAC (high glucose metabolism levels) and lipomet-PDAC (high lipid metabolism levels). Glucomet-PDACs are more resistant to chemotherapy than lipomet-PDACs, and patients with glucomet-PDAC have a worse prognosis. Integrated analyses reveal that the GLUT1/aldolase B (ALDOB)/glucose-6-phosphate dehydrogenase (G6PD) axis induces chemotherapy resistance by remodeling glucose metabolism in glucomet-PDAC. Increased glycolytic flux, G6PD activity, and pyrimidine biosynthesis are identified in glucomet-PDAC with high GLUT1 and low ALDOB expression, and these phenotypes could be reversed by inhibiting GLUT1 expression or by increasing ALDOB expression. Pharmacological inhibition of GLUT1 or G6PD enhances the chemotherapy response of glucomet-PDAC. Our findings uncover potential metabolic heterogeneity related to differences in chemotherapy sensitivity in PDAC and develop a promising pharmacological strategy for patients with chemotherapy-resistant glucomet-PDAC through the combination of chemotherapy and GLUT1/ALDOB/G6PD axis inhibitors.