ALDH1A1 in breast cancer: A prospective target to overcome therapy resistance (Review)

Oncology Letters, Journal Year: 2025, Volume and Issue: 29(5), P. 1 - 17

Published: March 4, 2025

The expression of cytosolic aldehyde dehydrogenases (ALDHs), which mediate the last step in pathway synthesis all‑trans retinoic acid, is dysregulated various types human cancer, and has been associated with development cancer stem cells (CSCs) solid tumors hematological malignancies. CSCs are considered a minor fraction capacity to initiate neoplastic tumors. ALDH1A1 serves crucial role emergence CSC phenotype, induces malignant behavior promotes treatment resistance. Notably, ALDH1A1‑induced therapy resistance not exclusive just one group drugs, but affects diverse drugs that use different mechanisms kill cells. This diversity drug resistance‑inducing effects stemness‑supporting functions ALDH1A1. inhibition activity using chemicals or depletion via genetic approaches, such as small interfering RNA, can overcome pathways In context breast it critical only expected manifest stem‑like features, include increased From angle disease prognosis, extent association remains be determined through application cutting‑edge methods detect tracked biomarkers within

Language: Английский

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Silica-induced ferroptosis activates retinoic acid signaling in dendritic cells to drive inflammation and fibrosis in silicosis

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 149, P. 114244 - 114244

Published: Feb. 11, 2025

Language: Английский

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Proteomics Profiling Reveals Pharmaceutical Excipient PEG400 Induces Nuclear-Receptor-Activation-Affected Lipid Metabolism and Metabolic Enzyme Expression

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1732 - 1732

Published: Feb. 18, 2025

PEG400 is widely used as a pharmaceutical excipient in the biomedical field. Increasing evidence suggests that not an inert drug carrier; it can influence activity of various drug-metabolizing enzymes and transporters, thereby affecting vivo process drugs. It also alleviate obesity adipose tissue inflammation induced by high-fat diet. In this study, we employed proteomics to investigate impact on hepatic protein expression rats. We found over 40 metabolic were altered, with UDP-glucuronosyltransferase 1a9 (Ugt1a9) showing most significant upregulation. This observation consistent our previous findings. KEGG pathway enrichment analysis revealed influences retinol metabolism, steroid hormone biosynthesis, bile secretion, fatty acid degradation, peroxisome proliferator-activated receptor (PPAR) signaling pathway, pentose glucuronate interconversions. Western blot molecular docking quantitatively analyze related proteins. The results demonstrated promotes metabolism produce retinoic acid; enhances secretion upregulating synthesis transporter proteins; activates PPARα regulate fat metabolism-related proteins, reducing lipid accumulation. Furthermore, natural ligands for nuclear receptors, acids may activate receptors initiate regulation target gene expression. upregulation PPARα, retinoid X alpha (RXRα), pregnane (PXR). RXRα form dimer or PXR genes, which explain changes numerous enzymes. study provides comprehensive understanding effects liver rats, reveals its potential biological functions, offers new insights into application development PEG400.

Language: Английский

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Circular RNAs modulate cancer drug resistance: advances and challenges

Cancer Drug Resistance, Journal Year: 2025, Volume and Issue: unknown

Published: March 28, 2025

Acquired drug resistance is a main factor contributing to cancer therapy failure and high mortality, highlighting the necessity develop novel intervention targets. Circular RNAs (circRNAs), an abundant class of RNA molecules with closed loop structure, possess characteristics including stability, which provide unique advantages in clinical application. Growing evidence indicates that aberrantly expressed circRNAs are associated against various treatments, targeted therapy, chemotherapy, radiotherapy, immunotherapy. Therefore, targeting these aberrant may offer strategy improve efficiency therapy. Herein, we present summary most recently studied their regulatory roles on resistance. With advances artificial intelligence (AI)-based bioinformatics algorithms, could emerge as promising biomarkers targets

Language: Английский

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Sarcosine sensitizes lung adenocarcinoma to chemotherapy by dual activation of ferroptosis via PDK4/PDHA1 signaling and NMDAR-mediated iron export

Experimental Hematology and Oncology, Journal Year: 2025, Volume and Issue: 14(1)

Published: April 24, 2025

Language: Английский

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The Role of Cancer Organoids in Ferroptosis, Pyroptosis, and Necroptosis: Functions and Clinical Implications

Biomolecules, Journal Year: 2025, Volume and Issue: 15(5), P. 659 - 659

Published: May 2, 2025

The enduring prevalence of cancer worldwide constitutes a significant public health challenge, thereby emphasizing the imperative for development therapeutic models capable accounting heterogeneity inherent in tumors. In this context, organoids have emerged as powerful tools studying tumor biology, providing valuable insights into complex interactions within microenvironment. Concurrently, research is increasingly focused on non-apoptotic forms regulated cell death (RCD)—including ferroptosis, pyroptosis, and necroptosis—which exert pivotal influences progression. Cancer not only recapitulate genetic phenotypic original tumors but also enable more precise investigations roles RCDs oncology. This review explores utility delineating molecular mechanisms underlying their implications biology treatment responses. By synthesizing recent findings, it highlights essential role organoid uncovering intricate details RCDs. Furthermore, emphasizes promising directions future that aim to deepen our understanding these pathways potential. integration necroptosis provides novel oncogenic facilitates targeted strategies. bridging with human pathophysiology, approach transformative framework dissecting enables design precision therapeutics selectively target machinery

Language: Английский

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Disruption of the sorcin‒PAX5 protein‒protein interaction induces ferroptosis by promoting the FBXL12-mediated ubiquitination of ALDH1A1 in pancreatic cancer

Journal of Hematology & Oncology, Journal Year: 2025, Volume and Issue: 18(1)

Published: March 7, 2025

Language: Английский

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