A stumbling block in pancreatic cancer treatment: drug resistance signaling networks

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 12

Published: Jan. 13, 2025

The primary node molecules in the cell signaling network cancer tissues are maladjusted and mutated comparison to normal tissues, which promotes occurrence progression of cancer. Pancreatic (PC) is a highly fatal with increasing incidence low five-year survival rates. Currently, there several therapies that target networks PC. However, PC "cold tumor" unique immunosuppressive tumor microenvironment (poor effector T infiltration, antigen specificity), targeting single gene or pathway basically ineffective clinical practice. Targeted matrix therapy, targeted metabolic mutant vaccines, other emerging have shown great therapeutic potential, but results been disappointing. Therefore, we summarize identified potential drug-resistant aimed at overcoming barriers existing therapies.

Language: Английский

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Linking macrophage metabolism to function in the tumor microenvironment

Nature Cancer, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 17, 2025

Language: Английский

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Exploiting the Achilles’ heel of cancer: disrupting glutamine metabolism for effective cancer treatment

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: March 6, 2024

Cancer cells have adapted to rapid tumor growth and evade immune attack by reprogramming their metabolic pathways. Glutamine is an important nitrogen resource for synthesizing amino acids nucleotides carbon source in the tricarboxylic acid (TCA) cycle lipid biosynthesis pathway. In this review, we summarize significant role of glutamine metabolism development highlight vulnerabilities targeting effective therapy. particular, review reported drugs glutaminase uptake efficient cancer treatment. Moreover, discuss current clinical test about prospective direction drug development.

Language: Английский

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The Tricarboxylic Acid Cycle Metabolites for Cancer: Friend or Enemy

Research, Journal Year: 2024, Volume and Issue: 7

Published: Jan. 1, 2024

The tricarboxylic acid (TCA) cycle is capable of providing sufficient energy for the physiological activities under aerobic conditions. Although tumor metabolic reprogramming places glycolysis in a dominant position, TCA remains indispensable cells as hub linkage and interconversion glucose, lipids, certain amino acids. intermediates such citrate, α-ketoglutarate, succinate, fumarate are altered tumors, they regulate metabolism, signal transduction, immune environment to affect tumorigenesis progression. This article provides comprehensive review modifications occurring relation cycle, which affects pathogenesis current therapeutic strategy therapy through targeting cancer cells.

Language: Английский

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Glutamine Metabolism and Prostate Cancer

Cancers, Journal Year: 2024, Volume and Issue: 16(16), P. 2871 - 2871

Published: Aug. 18, 2024

Glutamine (Gln) is a non-essential amino acid that involved in the development and progression of several malignancies, including prostate cancer (PCa). While Gln for non-malignant epithelial cells, PCa cells become highly dependent on an exogenous source Gln. The metabolism tightly controlled by well-described oncogenes such as MYC, AR, mTOR. These contribute to therapy resistance aggressive castration-resistant PCa. Inhibition catabolism impedes growth, survival, tumor-initiating potential while sensitizing radiotherapy. Therefore, given its significant role tumor targeting promising approach developing new therapeutic strategies. Ongoing clinical trials evaluate safety efficacy inhibitors combination with conventional targeted therapies patients various solid tumors, Further understanding how metabolically interact their microenvironment will facilitate translation help improve outcomes. This review focuses provides insights into current trials.

Language: Английский

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Glutamine analogs for pancreatic cancer therapy

Nature Cancer, Journal Year: 2024, Volume and Issue: 5(1), P. 2 - 4

Published: Jan. 30, 2024

Language: Английский

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Decoding the Intricate Landscape of Pancreatic Cancer: Insights into Tumor Biology, Microenvironment, and Therapeutic Interventions

Cancers, Journal Year: 2024, Volume and Issue: 16(13), P. 2438 - 2438

Published: July 2, 2024

Pancreatic ductal adenocarcinoma (PDAC) presents significant oncological challenges due to its aggressive nature and poor prognosis. The tumor microenvironment (TME) plays a critical role in progression treatment resistance. Non-neoplastic cells, such as cancer-associated fibroblasts (CAFs) tumor-associated macrophages (TAMs), contribute growth, angiogenesis, immune evasion. Although cells infiltrate TME, evade responses by secreting chemokines expressing checkpoint inhibitors (ICIs). Vascular components, like endothelial pericytes, stimulate angiogenesis support while adipocytes secrete factors that promote cell invasion, Additionally, perineural characteristic feature of PDAC, contributes local recurrence Moreover, key signaling pathways including Kirsten rat sarcoma viral oncogene (KRAS), transforming growth factor beta (TGF-β), Notch, hypoxia-inducible (HIF), Wnt/β-catenin drive Targeting the TME is crucial for developing effective therapies, strategies inhibiting CAFs, modulating response, disrupting blocking neural interactions. A recent multi-omic approach has identified signature genes associated with anoikis resistance, which could serve prognostic biomarkers targets personalized therapy.

Language: Английский

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Pancreatic ductal adenocarcinoma cells reshape the immune microenvironment: Molecular mechanisms and therapeutic targets

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2024, Volume and Issue: 1879(6), P. 189183 - 189183

Published: Sept. 19, 2024

Language: Английский

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Identification of Metabolic Characteristic–Pancreatic Ductal Adenocarcinoma Associations Using Mendelian Randomization and Metabolomics

Journal of Gastrointestinal Cancer, Journal Year: 2025, Volume and Issue: 56(1)

Published: Jan. 20, 2025

Language: Английский

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Identification of glutamine as a potential therapeutic target in dry eye disease

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Jan. 21, 2025

Abstract Dry eye disease (DED) is a prevalent inflammatory condition significantly impacting quality of life, yet lacks effective pharmacological therapies. Herein, we proposed novel approach to modulate the inflammation through metabolic remodeling, thus promoting dry recovery. Our study demonstrated that co-treatment with mesenchymal stem cells (MSCs) and thymosin beta-4 (Tβ4) yielded best therapeutic outcome against eye, surpassing monotherapy outcomes. In situ metabolomics matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) revealed increased glutamine levels in cornea following MSC + Tβ4 combined therapy. Inhibition reversed anti-inflammatory, anti-apoptotic, homeostasis-preserving effects observed therapy, highlighting critical role Clinical cases rodent model showed elevated expression glutaminase (GLS1), an upstream enzyme metabolism, injury. Mechanistic studies indicated overexpression inhibition GLS1 counteracted enhanced, respectively, anti-inflammatory underscoring GLS1’s pivotal regulating metabolism. Furthermore, single-cell sequencing distinct subset pro-inflammatory pro-fibrotic corneal epithelial model, while treatment downregulated those subclusters, thereby reducing their cytokine secretion. summary, effectively ameliorated occurrence apoptosis by downregulating subclusters related IκBα/NF-κB signaling. The present suggests metabolism plays critical, previously unrecognized DED proposes attractive strategy enhance inhibiting alleviating inflammation-driven progression.

Language: Английский

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