The language of chromatin modification in human cancers

Nature reviews. Cancer, Journal Year: 2021, Volume and Issue: 21(7), P. 413 - 430

Published: May 17, 2021

Language: Английский

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Epigenetic modulation of antitumor immunity for improved cancer immunotherapy

Molecular Cancer, Journal Year: 2021, Volume and Issue: 20(1)

Published: Dec. 20, 2021

Abstract Epigenetic mechanisms play vital roles not only in cancer initiation and progression, but also the activation, differentiation effector function(s) of immune cells. In this review, we summarize current literature related to epigenomic dynamics cells impacting cell fate functionality, immunogenicity Some important immune-associated genes, such as granzyme B, IFN-γ, IL-2, IL-12, FoxP3 STING, are regulated via epigenetic or/and cells, checkpoint molecules (PD-1, CTLA-4, TIM-3, LAG-3, TIGIT) expressed by tumor-associated stromal Thus, therapeutic strategies implementing modulating drugs expected significantly impact tumor microenvironment (TME) promoting transcriptional metabolic reprogramming local populations, resulting inhibition immunosuppressive (MDSCs Treg) activation anti-tumor T professional antigen presenting (APC), well which can serve non-professional APC. latter instance, agents may coordinately promote inducing de novo expression transcriptionally repressed antigens, increasing neoantigens MHC processing/presentation machinery, activating immunogenic death (ICD). ICD provides a rich source immunogens for cross-priming sensitizing interventional immunotherapy. way, modulators be envisioned effective components combination immunotherapy approaches capable mediating superior efficacy.

Language: Английский

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Epigenetic regulation in metabolic diseases: mechanisms and advances in clinical study

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: March 2, 2023

Abstract Epigenetics regulates gene expression and has been confirmed to play a critical role in variety of metabolic diseases, such as diabetes, obesity, non-alcoholic fatty liver disease (NAFLD), osteoporosis, gout, hyperthyroidism, hypothyroidism others. The term ‘epigenetics’ was firstly proposed 1942 with the development technologies, exploration epigenetics made great progresses. There are four main epigenetic mechanisms, including DNA methylation, histone modification, chromatin remodelling, noncoding RNA (ncRNA), which exert different effects on diseases. Genetic non-genetic factors, ageing, diet, exercise, interact jointly affect formation phenotype. Understanding could be applied diagnosing treating diseases clinic, biomarkers, drugs, editing. In this review, we introduce brief history well milestone events since proposal ‘epigenetics’. Moreover, summarise research methods general mechanisms modulation. Furthermore, interaction between genetic or factors. Finally, clinical trials applications

Language: Английский

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Emerging role of natural products in cancer immunotherapy

Acta Pharmaceutica Sinica B, Journal Year: 2021, Volume and Issue: 12(3), P. 1163 - 1185

Published: Aug. 21, 2021

Cancer immunotherapy has become a new generation of anti-tumor treatment, but its indications still focus on several types tumors that are sensitive to the immune system. Therefore, effective strategies can expand and enhance efficiency key element for further development cancer immunotherapy. Natural products reported have this effect immunotherapy, including vaccines, immune-check points inhibitors, adoptive immune-cells therapy. And mechanism is mainly attributed remodeling tumor-immunosuppressive microenvironment, which factor assists tumor avoid recognition attack from system review summarizes concludes natural reportedly improve investigates mechanism. we found saponins, polysaccharides, flavonoids three categories products, reflected significant effects combined with through reversing microenvironment. Besides, also collected studies about nano-technology used disadvantages products. All these showed great potential in

Language: Английский

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Protein tyrosine kinase inhibitor resistance in malignant tumors: molecular mechanisms and future perspective

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: Sept. 17, 2022

Abstract Protein tyrosine kinases (PTKs) are a class of proteins with kinase activity that phosphorylate residues critical molecules in signaling pathways. Their basal function is essential for maintaining normal cell growth and differentiation. However, aberrant activation PTKs caused by various factors can deviate from the expected trajectory to an abnormal state, leading carcinogenesis. Inhibiting PTK could inhibit tumor growth. Therefore, inhibitors (TKIs), target-specific PTKs, have been used treating malignant tumors play significant role targeted therapy cancer. Currently, drug resistance main reason limiting TKIs efficacy The increasing studies indicated microenvironment, death resistance, metabolism, epigenetic modification metabolism were deeply involved development TKI besides PTK-related pathways gene mutations. Accordingly, it great significance study underlying mechanisms find solutions reverse improving Herein, we reviewed potential approaches overcome aiming provide theoretical basis TKIs.

Language: Английский

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Targeting histone acetylation dynamics and oncogenic transcription by catalytic P300/CBP inhibition

Molecular Cell, Journal Year: 2021, Volume and Issue: 81(10), P. 2183 - 2200.e13

Published: May 1, 2021

To separate causal effects of histone acetylation on chromatin accessibility and transcriptional output, we used integrated epigenomic transcriptomic analyses following acute inhibition major cellular lysine acetyltransferases P300 CBP in hematological malignancies. We found that catalytic P300/CBP dynamically perturbs steady-state kinetics suppresses oncogenic networks the absence changes to accessibility. CRISPR-Cas9 screening identified NCOR1 HDAC3 co-repressors as principal antagonists by counteracting turnover kinetics. Finally, deacetylation H3K27 provides nucleation sites for reciprocal methylation switching, a feature can be exploited therapeutically concomitant KDM6A inhibition. Overall, this study indicates acetylation-methylation equilibrium functions molecular rheostat governing transcription is amenable therapeutic exploitation an anti-cancer regimen.

Language: Английский

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Eliminating METTL1‐mediated accumulation of PMN‐MDSCs prevents hepatocellular carcinoma recurrence after radiofrequency ablation

Hepatology, Journal Year: 2022, Volume and Issue: 77(4), P. 1122 - 1138

Published: May 22, 2022

Radiofrequency ablation (RFA) is an important curative therapy in hepatocellular carcinoma (HCC), but recurrence rate remains as high all the other HCC therapeutic modalities. Methyltransferase 1 (METTL1), enzyme for m 7 G tRNA modification, was reported to promote development. Here, we assessed role of METTL1 shaping immunosuppressive tumor microenvironment after insufficient RFA (iRFA).By immunohistochemistry and multiplex immunofluorescence (mIF) staining, showed that expression enhanced post-RFA recurrent HCC, accompanied by increased CD11b + CD15 polymorphonuclear-myeloid-derived suppressor cells (PMN-MDSCs) decreased CD8 T cells. Mechanistically, heat-mediated upregulation TGF-β2 translation form environment induction myeloid-derived cell. Liver-specific overexpression or knockdown Mettl1 significantly affected accumulation PMN-MDSCs subsequently cell infiltration. Complete successfully eliminated tumor, whereas iRFA-treated mice exhibited growth metastasis with PMN-MDSC compared sham surgery. Interrupting METTL1-TGF-β2-PMN-MDSC axis anti-Ly6G antibody, hepatoma-intrinsic Tgfb2 , TGF-β signaling blockade mitigated progression induced iRFA restored population.Our study sheds light on pivotal modulating demonstrated interrupting could be a strategy restore antitumor immunity prevent treatment, meriting further clinical studies.

Language: Английский

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Metabolic reprogramming and epigenetic modifications in cancer: from the impacts and mechanisms to the treatment potential

Experimental & Molecular Medicine, Journal Year: 2023, Volume and Issue: 55(7), P. 1357 - 1370

Published: July 3, 2023

Abstract Metabolic reprogramming and epigenetic modifications are hallmarks of cancer cells. In cells, metabolic pathway activity varies during tumorigenesis progression, indicating regulated plasticity. changes often closely related to changes, such as alterations in the expression or epigenetically modified enzymes, which may exert a direct an indirect influence on cellular metabolism. Therefore, exploring mechanisms underlying regulating tumor cell metabolism is important for further understanding pathogenesis. Here, we mainly focus latest studies regulations, including glucose, lipid amino acid context, then emphasize modifications. Specifically, discuss role played by DNA methylation, chromatin remodeling, noncoding RNAs histone lactylation growth progression. Finally, summarize prospects potential therapeutic strategies based

Language: Английский

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The hallmarks of cancer immune evasion

Cancer Cell, Journal Year: 2024, Volume and Issue: 42(11), P. 1825 - 1863

Published: Oct. 10, 2024

Language: Английский

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Small molecule inhibitors targeting the cancers

MedComm, Journal Year: 2022, Volume and Issue: 3(4)

Published: Oct. 13, 2022

Compared with traditional therapies, targeted therapy has merits in selectivity, efficacy, and tolerability. Small molecule inhibitors are one of the primary therapies for cancer. Due to their advantages a wide range targets, convenient medication, ability penetrate into central nervous system, many efforts have been devoted developing more small inhibitors. To date, 88 approved by United States Food Drug Administration treat cancers. Despite remarkable progress, cancer treatment still face obstacles, such as low response rate, short duration response, toxicity, biomarkers, resistance. better promote development targeting cancers, we comprehensively reviewed involved all agents pivotal drug candidates clinical trials arranged signaling pathways classification We discussed lessons learned from these agents, proper strategies overcome resistance arising different mechanisms, combination concerned Through our review, hoped provide insights perspectives research treatment.

Language: Английский

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