Recent Advances in Therapeutic Strategies to Improve Colorectal Cancer Treatment

Cancers, Год журнала: 2024, Номер 16(5), С. 1029 - 1029

Опубликована: Март 2, 2024

Colorectal cancer (CRC) is the second-leading cause of cancer-related mortality worldwide. CRC results almost exclusively from metastatic disease (mCRC) for which systemic chemotherapy often a preferred therapeutic option. Biomarker-based stratification mCRC enables use precision therapy based on individual tumor mutational profiles. Activating mutations in RAS/RAF/MAPK pathway downstream EGFR signaling have, until recently, limited EGFR-targeted therapies mCRC; however, development anti-RAS and anti-RAF together with improved strategies to limit compensatory pathways resulting survival rates several highly lethal sub-types (e.g., BRAF-mutant). The fluoropyrimidine (FP)-based regimens treat continues evolve contributing long-term survival. Future advances will need position relative made oncology.

Язык: Английский

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Triple coumarin-based 5-fluorouracil prodrugs, their synthesis, characterization, and release kinetics

Journal of Molecular Structure, Год журнала: 2023, Номер 1301, С. 137415 - 137415

Опубликована: Дек. 26, 2023

Язык: Английский

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Activation of sphingosine-1-phosphate receptor 2 (S1PR2) upregulates dihydropyrimidine dehydrogenase (DPD) expression in colon cancer cells

Journal of Advanced Research, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

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Energy Metabolism and Stemness and the Role of Lauric Acid in Reversing 5-Fluorouracil Resistance in Colorectal Cancer Cells

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(2), С. 664 - 664

Опубликована: Янв. 14, 2025

While 5-fluorouracil (5FU) plays a central role in chemotherapy for colorectal cancer (CRC), resistance to 5FU remains major challenge CRC treatment, and its underlying mechanisms remain unclear. In this study, we investigated the relationship between acquisition, stemness, energy metabolism. Among two cell lines, HT29 cells exhibited glycolytic quiescent properties, while CT26 relied on oxidative phosphorylation (OXPHOS) energy. contrast, 5FU-resistant sublines (HT29R CT26R), developed through continuous exposure low concentrations of 5FU, demonstrated enhanced stemness. This was associated with dominance, proliferation, reduced reactive oxygen species (ROS) production. However, treatment medium-chain fatty acid lauric shifted OXPHOS, reducing increasing ROS levels, inducing death, therefore reversing resistance. These findings suggest that an enhancement stemness reprogramming metabolism play key roles acquiring CRC. reversed resistance, further clinical studies are required.

Язык: Английский

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HDAC3-Mediated Deacetylation of p21 Stabilizes Protein Levels and Promotes 5-FU Resistance in Colorectal Cancer Cells

Advances in Cancer Biology - Metastasis, Год журнала: 2025, Номер unknown, С. 100136 - 100136

Опубликована: Фев. 1, 2025

Язык: Английский

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Drug resistance in human cancers — Mechanisms and implications

Life Sciences, Год журнала: 2024, Номер 352, С. 122907 - 122907

Опубликована: Июль 14, 2024

Язык: Английский

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A Proteomic Investigation to Discover Candidate Proteins Involved in Novel Mechanisms of 5-Fluorouracil Resistance in Colorectal Cancer

Cells, Год журнала: 2024, Номер 13(4), С. 342 - 342

Опубликована: Фев. 14, 2024

One of the main obstacles to therapeutic success in colorectal cancer (CRC) is development acquired resistance treatment with drugs such as 5-fluorouracil (5-FU). Whilst some mechanisms are well known, it clear from stasis therapy rate that much still unknown. Here, a proteomics approach taken towards identification candidate proteins using 5-FU-resistant sublines human CRC cell lines generated house. Using multiplexed stable isotope labelling amino acids culture (SILAC) strategy, and equivalently passaged sensitive were compared parent by growing Heavy medium 2D liquid chromatography Orbitrap Fusion™ Tribrid™ Mass Spectrometry analysis. Among 3003 commonly quantified proteins, six (CD44, APP, NAGLU, CORO7, AGR2, PLSCR1) found up-regulated, (VPS45, RBMS2, RIOK1, RAP1GDS1, POLR3D, CD55) down-regulated. A total 11 12 have known association drug or role oncogenesis. Validation through immunodetection techniques confirmed high expression CD44 CD63, two mediators elevated results. The information revealed sensitivity this method warrants an important tool for elaborating complexity CRC.

Язык: Английский

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Ataxia telangiectasia and Rad3-related (ATR) inhibition by VE-822 potently reversed 5-flourouracil resistance in colorectal cancer cells through targeting DNA damage response

Molecular Biology Reports, Год журнала: 2024, Номер 51(1)

Опубликована: Март 29, 2024

Язык: Английский

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Squalene epoxidase promotes the chemoresistance of colorectal cancer via (S)-2,3-epoxysqualene-activated NF-κB

Cell Communication and Signaling, Год журнала: 2024, Номер 22(1)

Опубликована: Май 18, 2024

Abstract Background While de novo cholesterol biosynthesis plays a crucial role in chemotherapy resistance of colorectal cancer (CRC), the underlying molecular mechanism remains poorly understood. Methods We conducted cell proliferation assays on CRC cells with or without depletion squalene epoxidase (SQLE), 5-fluorouracil (5-FU) treatment. Additionally, xenograft mouse model was utilized to explore impact SQLE chemosensitivity 5-FU. RNA-sequencing analysis and immunoblotting were performed clarify mechanism. further effect ubiquitin NF-κB inhibitor alpha (IκBα) (S)-2,3-epoxysqualene binding IκBα beta-transducin repeat containing E3 protein ligase (BTRC) by using immunoprecipitation assay. In addition, cohort 272 patients selected for our clinical analyses. Results Mechanistically, promotes degradation subsequent activation enhancing interaction between BTRC IκBα. Activated upregulates expression baculoviral IAP 3 (BIRC3), sustains tumor survival after 5-FU treatment vivo. Notably, terbinafine, an commonly used as antifungal drug clinic, enhances sensitivity is associated prognosis human 5-FU-based chemotherapy. Conclusions Thus, finding not only demonstrates new chemoresistance CRC, but also reveals novel (S)-2,3-epoxysqualene-dependent activation, implicating combined potential terbinafine

Язык: Английский

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Regulatory role of non-coding RNAs in 5-Fluorouracil resistance in gastrointestinal cancers

Cancer Drug Resistance, Год журнала: 2025, Номер unknown

Опубликована: Янв. 16, 2025

Gastrointestinal (GI) cancers are becoming a growing cause of morbidity and mortality globally, posing significant risk to human life health. The main treatment for this kind cancer is chemotherapy based on 5-fluorouracil (5-FU). However, the issue 5-FU resistance increasingly prominent, which greatly limits its effectiveness in clinical treatment. Recently, numerous studies have disclosed that some non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long (lncRNAs), circular (circRNAs), exert remarkable physiological functions within cells. In addition, these ncRNAs can also serve as important information communication molecules tumor microenvironment regulate resistance. particular, they been shown play multiple roles regulating GI cancers. Herein, we summarize targets, pathways, mechanisms involved by briefly discuss application potential biomarkers or therapeutic targets cancers, aiming offer reference tackle issues related

Язык: Английский

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