Metabolic reprogramming based on RNA sequencing of gemcitabine-resistant cells reveals the FASN gene as a therapeutic for bladder cancer

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: Jan. 13, 2024

Abstract Bladder cancer (BLCA) is the most frequent malignant tumor of genitourinary system. Postoperative chemotherapy drug perfusion and are important means for treatment BLCA. However, once resistance occurs, BLCA develops rapidly after recurrence. cells rely on unique metabolic rewriting to maintain their growth proliferation. relationship between pattern changes in unclear. At present, this problem lacks systematic research. In our research, we identified analyzed resistance- metabolism-related differentially expressed genes (RM-DEGs) based RNA sequencing a gemcitabine-resistant cell line metabolic-related (MRGs). Then, established model (RM-RM) through regression analysis predict overall survival We also confirmed that RM-RM had significant correlation with metabolism, gene mutations, microenvironment, adverse reactions. Patients high risk score (RM-RS) showed more active lipid synthesis than those low RM-RS. Further vitro vivo studies were implemented using Fatty Acid Synthase (FASN), representative gene, which promotes gemcitabine resistance, its inhibitor (TVB-3166) can reverse effect.

Language: Английский

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Fundamental insights and molecular interactions in pancreatic cancer: Pathways to therapeutic approaches

Cancer Letters, Journal Year: 2024, Volume and Issue: 588, P. 216738 - 216738

Published: Feb. 23, 2024

Language: Английский

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Inhibitors of the Cancer Target Ribonucleotide Reductase, Past and Present

Biomolecules, Journal Year: 2022, Volume and Issue: 12(6), P. 815 - 815

Published: June 10, 2022

Ribonucleotide reductase (RR) is an essential multi-subunit enzyme found in all living organisms; it catalyzes the rate-limiting step dNTP synthesis, namely, conversion of ribonucleoside diphosphates to deoxyribonucleoside diphosphates. As expression levels human RR (hRR) are high during cell replication, hRR has long been considered attractive drug target for a range proliferative diseases, including cancer. While there many excellent reviews regarding structure, function, and clinical importance hRR, recent years have seen increase novel approaches inhibiting that merit updated discussion existing inhibitors strategies this enzyme. In review, we discuss mechanisms applications classic nucleoside analog hRRM1 (large catalytic subunit), gemcitabine clofarabine, as well hRRM2 (free radical housing small triapine hydroxyurea. Additionally, targeting discovery new classes inhibitors.

Language: Английский

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Dysregulated Signalling Pathways Driving Anti-cancer Drug Resistance

Published: July 19, 2023

One of the leading causes death worldwide, in both man and woman, is cancer. Despite significant development therapeutic strategies, inevitable emergence drug resistance limits success impedes curative outcome. Intrinsic acquired are common mechanisms responsible for cancer relapse. Several factors crucially regulate tumourigenesis resistance, including physical barriers, tumour microenvironment (TME), heterogeneity, genetic epigenetic alterations, immune system, burden, growth kinetics undruggable targets. Moreover, transforming factor-beta (TGF-β), Notch, epidermal factor receptor (EGFR), integrin-extracellular matrix (ECM), nuclear kappa-light-chain-enhancer activated B cells (NF-κB), phosphoinositol-3-kinase/protein kinase B/mammalian target rapamycin (PI3K/Akt/mTOR), wingless-related integration site (Wnt)/β-catenin), Janus kinase/signal transducers activators transcription (JAK/STAT) RAS/RAF/mitogen-activated protein (MAPK) signalling pathways some key players that have a pivotal role mechanisms. To guide future treatments improve results, deeper comprehension necessary. This review will cover intrinsic give comprehensive overview recent research on enable to bypass barriers put by treatments, like “satellite navigation”, find alternative routes carry their “journey” progression.

Language: Английский

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Acquired and intrinsic gemcitabine resistance in pancreatic cancer therapy: Environmental factors, molecular profile and drug/nanotherapeutic approaches

Environmental Research, Journal Year: 2023, Volume and Issue: 240, P. 117443 - 117443

Published: Oct. 18, 2023

Language: Английский

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Terpenoids from quinoa reverse drug resistance of colon cancer by upregulating miR‐495‐3p

Journal of the Science of Food and Agriculture, Journal Year: 2024, Volume and Issue: 104(14), P. 8916 - 8927

Published: July 4, 2024

Quinoa contains far more nutrients than any traditional grain crop. It is known that terpenoids in quinoa have anti-inflammatory and antitumor effects, but their role reversing drug resistance remains unclear.

Language: Английский

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Investigating the regulatory role of miRNAs as silent conductors in the management of pathogenesis and therapeutic resistance of pancreatic cancer

Pathology - Research and Practice, Journal Year: 2023, Volume and Issue: 251, P. 154855 - 154855

Published: Oct. 5, 2023

Language: Английский

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Non-coding RNAs’ function in cancer development, diagnosis and therapy

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 167, P. 115527 - 115527

Published: Sept. 24, 2023

While previous research on cancer biology has focused genes that code for proteins, in recent years it been discovered non-coding RNAs (ncRNAs)play key regulatory roles cell biological functions. NcRNAs account more than 95% of human transcripts and are an important entry point the study mechanism development. An increasing number studies have demonstrated ncRNAs can act as tumor suppressor or oncogenes to regulate development at epigenetic level, transcriptional well post-transcriptional level. Because importance cancer, most clinical trials explore whether be used new biomarkers therapies. In this review, we focus including microRNAs (miRNAs), long (lncRNAs), circle (circRNAs), PIWI interacting (piRNAs), tRNA different types application these identification relevant therapeutic targets biomarkers. Graphical abstract drawn by Fidraw.

Language: Английский

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Molecular subtypes based on cuproptosis-related genes and tumor microenvironment infiltration characteristics in pancreatic adenocarcinoma

Cancer Cell International, Journal Year: 2023, Volume and Issue: 23(1)

Published: Jan. 16, 2023

Abstract Background Multiple molecular subtypes with distinct clinical outcomes in pancreatic adenocarcinoma (PAAD) have been identified recent years. Cuproptosis is a new form of cell death that likely involved tumor progression. However, the cuproptosis-related as well its mediated microenvironment (TME) infiltration characteristics largely remain unclear. Methods Expression profiles 10 genes (CRGs) and their association patient survival, TME, cancer stemness drug resistance were studied 33 types using TCGA pan-cancer data. Using 437 PAAD samples from five cohorts (TCGA-PAAD cohort four GEO cohorts), we explored by CRGs, along associated TME infiltration. Unsupervised methods utilized to perform cuproptosis subtype clustering. The score was constructed COX regression model least absolute shrinkage selection operator (LASSO) algorithm quantify single tumor. Results expression CRGs varies different striking inter- intra- heterogeneity. We integrated genomic profiling three subtypes, found multi-layer CRG alterations correlated prognosis characteristics. In addition, signature predict prognosis, impacts characterized TCGA-PAAD cohort. significantly CD8 T-cell infiltration, response immune checkpoint inhibitors (ICIs) chemotherapeutic sensitivity. Furthermore, patterns cells normal controls validated, which almost consistent results public database. level prognostic predictive capability DLAT verified 97 patients our Conclusions These findings may help understand roles characterization subtypes. could serve promising biomarker for predicting immunotherapy patients.

Language: Английский

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microRNAs Associated with Gemcitabine Resistance via EMT, TME, and Drug Metabolism in Pancreatic Cancer

Cancers, Journal Year: 2023, Volume and Issue: 15(4), P. 1230 - 1230

Published: Feb. 15, 2023

Despite extensive research, pancreatic cancer remains a lethal disease with an extremely poor prognosis. The difficulty in early detection and chemoresistance to therapeutic agents are major clinical concerns. To improve prognosis, novel biomarkers, strategies for urgently needed. microRNAs (miRNAs) play important roles the development, progression, metastasis of several cancers. During last few decades, association between miRNAs has been extensively elucidated, found be correlated patient Moreover, recent evidence revealed that intimately involved gemcitabine sensitivity resistance through epithelial-to-mesenchymal transition, tumor microenvironment, drug metabolism. Gemcitabine is gold standard treatment, but develops easily after chemotherapy initiation. Therefore, this review, we summarize mechanisms associated aberrantly expressed cancer, especially focusing on This will drive further research elucidate outcomes.

Language: Английский

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