Emerging mechanisms and promising approaches in pancreatic cancer metabolism

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(8)

Published: Aug. 1, 2024

Abstract Pancreatic cancer is an aggressive with a poor prognosis. Metabolic abnormalities are one of the hallmarks pancreatic cancer, and cells can adapt to biosynthesis, energy intake, redox needs through metabolic reprogramming tolerate nutrient deficiency hypoxic microenvironments. use glucose, amino acids, lipids as maintain malignant growth. Moreover, they also metabolically interact in tumour microenvironment change cell fate, promote progression, even affect immune responses. Importantly, changes at body level deserve more attention. Basic research clinical trials based on targeted therapy or combination other treatments full swing. A comprehensive in-depth understanding regulation will not only enrich mechanisms disease progression but provide inspiration for new diagnostic therapeutic approaches.

Language: Английский

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Recent Progress in the Development of Glucose Transporter (GLUT) Inhibitors

Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 2, 2025

Cancer cells exhibit an accelerated glucose uptake and glycolysis. The transmembrane of requires specific carrier proteins, such as transporters (GLUTs) sodium-coupled cotransporters (SGLTs). GLUTs transport independently the energy supply have become promising targets for cancer therapy. This Perspective mainly focuses on current research progress design strategy GLUT inhibitors, particularly those targeting class I (GLUT1–4). To best our knowledge, this is first systematic interpretation progress, opportunities, challenges faced in development inhibitors from a medicinal chemistry perspective. We hope that will provide insights into offering feasible approach to

Language: Английский

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Inflammation, microbiota, and pancreatic cancer

Cancer Cell International, Journal Year: 2025, Volume and Issue: 25(1)

Published: Feb. 22, 2025

Pancreatic cancer (PC) is a malignancy of gastrointestinal tract threatening the life people around world. In spite advances in treatment PC, overall survival this disease advanced stage less than 12%. Moreover, PC cells have aggressive behaviour proliferation and metastasis as well capable developing therapy resistance. Therefore, highlighting underlying molecular mechanisms pathogenesis can provide new insights for its treatment. present review, inflammation related pathways role gut microbiome regulation are highlighted. The various kinds interleukins chemokines able to regulate angiogenesis, metastasis, proliferation, resistance cells. Furthermore, number including NF-κB, TLRs TGF-β demonstrate dysregulation aggravating tumorigenesis. Therapeutic these reverse progression PC. Both chronic acute pancreatitis been shown be risk factors development further inflammation. Finally, composition microbiota factor through affecting such NF-κB mediate

Language: Английский

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Depletion of tumor-derived CXCL5 improves T cell infiltration and anti-PD-1 therapy response in an obese model of pancreatic cancer

Journal for ImmunoTherapy of Cancer, Journal Year: 2025, Volume and Issue: 13(3), P. e010057 - e010057

Published: March 1, 2025

Background CXCR1/2 inhibitors are being implemented with immunotherapies in PDAC clinical trials. CXC-ligands a family of cytokines responsible for stimulating these receptors; while typically secreted by activated immune cells, fibroblasts, and even adipocytes, they also immune-evasive cancer cells. CXC-ligand release is known to occur response inflammatory stimuli. Adipose tissue an endocrine organ source signaling peptides. Importantly, adipose-derived chemokines implicated as potential drivers tumor cell evasion; cumulatively, findings suggest that targeting may be beneficial the context obesity. Methods RNA-sequencing human lines was used assess influences adipose conditioned media on transcriptome. The adipose-induced secretome cells validated ELISA induction CXCL5 secretion. Human data from CPTAC correlate IL-1β TNF expression both mRNA protein levels. CRISPR-Cas9 knockout murine KPC line orthotopic studies syngeneic, diet-induced obese mice. Flow cytometry immunohistochemistry were compare profiles between tumors or without CXCL5. Mice-bearing competent deficient monitored differential size anti-PD-1 checkpoint blockade therapy. Results stimulates secretion via either TNF; neutralization required significantly block Ablation promoted enriched phenotype unanticipatedly increased number exhausted CD8 T Application treatment control failed alter growth, yet CXCL5-deficient showed diminished mass. Conclusions In summary, our show can stimulate vitro, which correlates patient data. depletion vivo alone sufficient promote infiltration into tumors, increasing efficacy requiring inhibition alleviate burden.

Language: Английский

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Chemokines: Orchestration of the Tumor Microenvironment and Control of Hepatocellular Carcinoma Progression

Cancer Medicine, Journal Year: 2025, Volume and Issue: 14(7)

Published: March 27, 2025

ABSTRACT Chemokines, a family of chemotactic cytokines, play central role in shaping the tumor microenvironment (TME) and influencing progression hepatocellular carcinoma (HCC), well‐known inflammation‐related cancer. This review addresses intricate interplay between chemokines HCC highlights their multifaceted role. We discuss how altered expression within TME contributes to development by orchestrating recruitment immune cells, ultimately leading immunosuppression. In addition, we are investigating contribution important features progression, including angiogenesis epithelial‐mesenchymal transition (EMT). The potential as serum biomarkers for diagnosis novel therapeutic targets also explored. comprehensive emphasizes importance pathogenesis better understanding treatment this difficult disease.

Language: Английский

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STAT3/TGFBI signaling promotes the temozolomide resistance of glioblastoma through upregulating glycolysis by inducing cellular senescence

Cancer Cell International, Journal Year: 2025, Volume and Issue: 25(1)

Published: April 3, 2025

Glioblastoma (GBM) is the most lethal type of brain tumor. Recent studies have indicated that cellular senescence-targeted therapy a promising approach for cancer treatment. However, underlying mechanisms remain to be clarified. In this study, 101 unique combinations 10 machine learning algorithms were used construct prognostic models based on senescence-related genes (CSRGs). We developed CSRG signature (CSRGS) using exhibited optimal performance. GBM samples stratified into high- and low-CSRGS groups CSRGS scores. Patients in high-CSRGS group worse prognosis, higher immune infiltration, increased sensitivity checkpoint blockade therapy. Furthermore, pathways significantly correlated with glycolysis, indicating upregulated glycolytic metabolism senescent cells. identified TGFBI as key regulator played vital roles both glycolysis senescence GBM. was overexpressed compared normal tissues, its knockdown via shRNA inhibited senescence, temozolomide resistance. Chromatin immunoprecipitation (ChIP) luciferase reporter assays confirmed direct STAT3 target required STAT3-induced promotion drug The STAT3-TGFBI axis could potential

Language: Английский

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Immunometabolism of Innate Immune Cells in Gastrointestinal Cancer

Cancers, Journal Year: 2025, Volume and Issue: 17(9), P. 1467 - 1467

Published: April 27, 2025

Cancer cells are often described as voracious consumers of nutrients, with glucose frequently cited a key energy source; however, their metabolic plasticity allows them to adapt and utilize various substrates, including lipids amino acids, sustain growth survival. However, the demands immune within tumor microenvironment (TME) less commonly discussed despite critical role in shaping response. In this review, we explored intricate interplay between immunometabolism innate immunity gastrointestinal cancers. We focused on how pathways, glycolysis, fatty acid oxidation, metabolism, drive immunosuppressive functions myeloid-derived suppressor (MDSCs) tumor-associated neutrophils (TANs), macrophages (TAMs) lymphocyte subsets such NK cells. These contribute hostile landscape, supporting evasion from surveillance phenomenon tumor-derived immunosuppression. Additionally, investigated influence dietary interventions reprogramming these cells, highlighting nutrition can modulate TME. Finally, emerging therapeutic strategies that target vulnerabilities MDSCs, TANs, monocytes, offering novel avenue for enhancing antitumor immunity. By dissecting mechanisms, aim provide insights into pathways be harnessed improve cancer treatment outcomes. This review underscores importance understanding not only driver suppression but also potential cancer.

Language: Английский

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Enhanced cytokine signaling and ferroptosis defense interplay initiates obesity-associated pancreatic ductal adenocarcinoma

Cancer Letters, Journal Year: 2024, Volume and Issue: 601, P. 217162 - 217162

Published: Aug. 9, 2024

Language: Английский

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