Human Genomics, Journal Year: 2024, Volume and Issue: 18(1)
Published: June 12, 2024
The insulin-like growth factor-2 mRNA-binding proteins 1, 2, and 3 (IGF2BP1, IGF2BP2, IGF2BP3) are known to be involved in tumorigenesis, metastasis, prognosis, cancer immunity various human cancers, including non-small cell lung (NSCLC). However, the literature on NSCLC largely omits specific context of squamous carcinoma (LUSC), an oversight we aim address.
Language: Английский
Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 169, P. 115891 - 115891
Published: Nov. 16, 2023
Lung cancer accounts for a relatively high proportion of malignant tumors. As the most prevalent type lung cancer, non-small cell (NSCLC) is characterized by morbidity and mortality. Presently, arsenal treatment strategies encompasses surgical resection, chemotherapy, targeted therapy radiotherapy. However, despite these options, prognosis remains distressingly poor with low 5-year survival rate. Therefore, it urgent to pursue paradigm shift in methodologies. In recent years, advent sophisticated biotechnologies interdisciplinary integration has provided innovative approaches cancer. This article reviews cutting-edge developments nano drug delivery system, molecular photothermal strategy, immunotherapy Overall, systematically summarizing critically analyzing latest progress current challenges we aim provide theoretical basis development novel drugs treatment, thus improve therapeutic outcomes patients.
Language: Английский
Citations
139
Cell Metabolism, Journal Year: 2024, Volume and Issue: 36(8), P. 1696 - 1710.e10
Published: Aug. 1, 2024
Patients with high ALDH1A3-expressing glioblastoma (ALDH1A3hi GBM) show limited benefit from postoperative chemoradiotherapy. Understanding the mechanisms underlying such resistance in these patients is crucial for development of new treatments. Here, we that interaction between ALDH1A3 and PKM2 enhances latter's tetramerization promotes lactate accumulation stem cells (GSCs). By scanning lactylated proteome lactate-accumulating GSCs, XRCC1 undergoes lactylation at lysine 247 (K247). Lactylated shows a stronger affinity importin α, allowing greater nuclear transposition enhanced DNA repair. Through high-throughput screening small-molecule library, D34-919 potently disrupts ALDH1A3-PKM2 interaction, preventing ALDH1A3-mediated enhancement tetramerization. In vitro vivo treatment chemoradiotherapy-induced apoptosis GBM cells. Together, our findings potential therapeutic target to improve response chemoradiotherapy ALDH1A3hi GBM.
Language: Английский
Citations
37
Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)
Published: Aug. 30, 2024
Drug resistance in cancer cells significantly diminishes treatment efficacy, leading to recurrence and metastasis. A critical factor contributing this is the epigenetic alteration of gene expression via RNA modifications, such as N6-methyladenosine (m6A), N1-methyladenosine (m1A), 5-methylcytosine (m5C), 7-methylguanosine (m7G), pseudouridine (Ψ), adenosine-to-inosine (A-to-I) editing. These modifications are pivotal regulating splicing, translation, transport, degradation, stability. Governed by "writers," "readers," "erasers," impact numerous biological processes progression, including cell proliferation, stemness, autophagy, invasion, apoptosis. Aberrant can lead drug adverse outcomes various cancers. Thus, targeting modification regulators offers a promising strategy for overcoming enhancing efficacy. This review consolidates recent research on role prevalent resistance, with focus m6A, m1A, m5C, m7G, Ψ, A-to-I Additionally, it examines regulatory mechanisms linked underscores existing limitations field.
Language: Английский
Citations
18
Advanced Science, Journal Year: 2024, Volume and Issue: unknown
Published: Oct. 25, 2024
Abstract Acquired resistance remains a bottleneck for molecular‐targeted therapy in advanced hepatocellular carcinoma (HCC). Metabolic adaptation and epigenetic remodeling are recognized as hallmarks of cancer that may contribute to acquired resistance. In various lenvatinib‐resistant models, increased glycolysis leads lactate accumulation lysine lactylation IGF2BP3. This is crucial capturing PCK2 NRF2 mRNAs, thereby enhancing their expression. process reprograms serine metabolism strengthens the antioxidant defense system. Additionally, altered increases availability methylated substrates, such S‐adenosylmethionine (SAM), N6‐methyladenosine (m6A) methylation mRNAs. The lactylated IGF2BP3‐PCK2‐SAM‐m6A loop maintains elevated levels, system promoting lenvatinib HCC. Treatment with liposomes carrying siRNAs targeting IGF2BP3 or inhibitor 2‐DG restored sensitivity vivo. These findings highlight connection between metabolic reprogramming regulation suggest pathways offer new strategies overcome
Language: Английский
Citations
18
Translational research, Journal Year: 2024, Volume and Issue: 268, P. 28 - 39
Published: Jan. 26, 2024
Language: Английский
Citations
13
Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)
Published: May 6, 2024
As the most common form of epigenetic regulation by RNA, N
Language: Английский
Citations
12
Heliyon, Journal Year: 2024, Volume and Issue: 10(5), P. e27207 - e27207
Published: March 1, 2024
Cancer drug resistance stands as a formidable obstacle in the relentless fight against top five prevalent cancers: breast, lung, colorectal, prostate, and gastric cancers. These malignancies collectively account for significant portion of cancer-related deaths worldwide. In recent years, long non-coding RNAs (lncRNAs) have emerged pivotal players intricate landscape cancer biology, their roles driving are steadily coming to light. This comprehensive review seeks underscore paramount significance lncRNAs orchestrating across spectrum different drugs, including platinum drugs (DDP), tamoxifen, trastuzumab, 5-fluorouracil (5-FU), paclitaxel (PTX), Androgen Deprivation Therapy (ADT) most types cancer. It delves into multifaceted mechanisms through which exert influence on resistance, shedding light regulatory various facets biology. A understanding these lncRNA-mediated may pave way more effective personalized treatment strategies, ultimately improving patient outcomes challenging malignancies.
Language: Английский
Citations
8
Gut, Journal Year: 2023, Volume and Issue: 73(6), P. 966 - 984
Published: Nov. 24, 2023
Objectives Cholangiocarcinoma (CCA) is a heterogeneous malignancy with high mortality and dismal prognosis, an urgent clinical need for new therapies. Knowledge of the CCA epigenome largely limited to aberrant DNA methylation. Dysregulation enhancer activities has been identified affect carcinogenesis leveraged therapies but uninvestigated in CCA. Our aim identify potential therapeutic targets different subtypes through profiling. Design Integrative multiomics activity profiling diverse was performed. A panel cell lines, patient-derived line-derived xenografts were used study enriched pathways vulnerabilities. NanoString, multiplex immunohistochemistry staining single-cell spatial transcriptomics explore immunogenicity Results We three distinct groups, associated etiologies unique pathways. Drug inhibitors reduced tumour growth vitro vivo models. The first group (ESTRO), mostly fluke-positive CCAs, displayed activation estrogen signalling sensitive MTOR inhibitors. Another (OXPHO), BAP1 IDH -mutant activated oxidative phosphorylation pathways, Immune-related final (IMMUN), made up immunogenic subtype aristolochic acid (AA) mutational signatures. Intratumour differences AA mutation load correlated intratumour variation immune populations. Conclusion elucidates mechanisms underlying dysregulation deepens understanding tumourigenesis processes subtypes, significant therapeutics benefits.
Language: Английский
Citations
13
European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 268, P. 116241 - 116241
Published: Feb. 15, 2024
Language: Английский
Citations
5
Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)
Published: Aug. 15, 2024
Abstract Third-generation EGFR tyrosine kinase inhibitors (TKIs), exemplified by osimertinib, have demonstrated promising clinical efficacy in the treatment of non-small cell lung cancer (NSCLC). Our previous work has identified ASK120067 as a novel third-generation TKI with remarkable antitumor effects that undergone New Drug Application (NDA) submission China. Despite substantial progress, acquired resistance to EGFR-TKIs remains significant challenge, impeding long-term effectiveness therapeutic approaches. In this study, we conducted comprehensive investigation utilizing high-throughput proteomics analysis on established TKI-resistant tumor models, and found notable upregulation branched-chain amino acid transaminase 1 (BCAT1) expression both osimertinib- ASK120067-resistant tumors compared parental TKI-sensitive NSCLC tumors. Genetic depletion or pharmacological inhibition BCAT1 impaired growth resistant cells partially re-sensitized TKIs. Mechanistically, upregulated reprogrammed (BCAA) metabolism promoted alpha ketoglutarate (α-KG)-dependent demethylation lysine 27 histone H3 (H3K27) subsequent transcriptional derepression glycolysis-related genes, thereby enhancing glycolysis promoting progression. Moreover, WQQ-345 inhibitor exhibiting activity vitro vivo against high expression. summary, our study highlighted crucial role mediating through epigenetic activation NSCLC, supporting target for NSCLC.
Language: Английский
Citations
5