Targeting one‐carbon metabolism for cancer immunotherapy DOI Creative Commons
Xinxin Ren, Xiang Wang, Guowan Zheng

et al.

Clinical and Translational Medicine, Journal Year: 2024, Volume and Issue: 14(1)

Published: Jan. 1, 2024

Abstract Background One‐carbon (1C) metabolism is a metabolic network that plays essential roles in biological reactions. In 1C metabolism, series of nutrients are used to fuel pathways, including nucleotide amino acid cellular redox defence and epigenetic maintenance. At present, considered the hallmark cancer. The units obtained from pathways increase proliferation rate cancer cells. addition, anticancer drugs, such as methotrexate, which target have long been clinic. terms immunotherapy, has explore biomarkers connected with immunotherapy response immune‐related adverse events patients. Methods We collected numerous literatures explain one‐carbon immunotherapy. Results this review, we focus on important function enzymes Then, summarise inhibitors acting their potential application Finally, provide viewpoint conclusion regarding opportunities challenges targeting for clinical practicability future. Conclusion Targeting useful

Language: Английский

Epigenetic Alterations in Triple-Negative Breast Cancer—The Critical Role of Extracellular Matrix DOI Open Access

Vasiliki Zolota,

Vassiliki Tzelepi, Zoi Piperigkou

et al.

Cancers, Journal Year: 2021, Volume and Issue: 13(4), P. 713 - 713

Published: Feb. 9, 2021

Triple-negative breast cancer (TNBC) is an aggressive subgroup of characterized by genomic complexity and therapeutic options limited to only standard chemotherapy. Although it has been suggested that stratifying TNBC patients pathway-specific molecular alterations may predict benefit from specific agents, application in routine clinical practice not yet established. There a growing body the literature supporting epigenetic modifications comprised DNA methylation, chromatin remodeling non-coding RNAs play fundamental role pathogenesis. Extracellular matrix (ECM) highly dynamic 3D network macromolecules with structural cellular regulatory roles. Alterations expression ECM components result uncontrolled remodeling, thus affecting its ability regulate vital functions cells, including proliferation, migration, adhesion, invasion epithelial-to-mesenchymal transition (EMT). Recent data highlight major tumor microenvironment approaches for targeting have recently recognized as potential strategies. Notably, many ECM/EMT are largely driven events, highlighting pleiotropic effects TNBC. This article presents critically discusses current knowledge on correlated pathogenesis, emphasis those associated modifications, their prognostic predictive value use targets.

Language: Английский

Citations

59
DNMT1-mediated epigenetic silencing of TRAF6 promotes prostate cancer tumorigenesis and metastasis by enhancing EZH2 stability DOI
Zhongwei Li,

Bingheng Li,

Haiyuan Yu

et al.

Oncogene, Journal Year: 2022, Volume and Issue: 41(33), P. 3991 - 4002

Published: July 8, 2022

Language: Английский

Citations

45
GSK-3484862 targets DNMT1 for degradation in cells DOI Creative Commons
Qin Chen,

Bigang Liu,

Yang Zeng

et al.

NAR Cancer, Journal Year: 2023, Volume and Issue: 5(2)

Published: March 11, 2023

Maintenance of genomic methylation patterns at DNA replication forks by DNMT1 is the key to faithful mitotic inheritance. often overexpressed in cancer cells and hypomethylating agents azacytidine decitabine are currently used treatment hematologic malignancies. However, toxicity these cytidine analogs their ineffectiveness treating solid tumors have limited wider clinical use. GSK-3484862 a newly-developed, dicyanopyridine containing, non-nucleoside DNMT1-selective inhibitor with low cellular toxicity. Here, we show that targets for protein degradation both cell lines murine embryonic stem (mESCs). depletion was rapid, taking effect within hours following treatment, leading global hypomethylation. Inhibitor-induced proteasome-dependent, no discernible loss mRNA. In mESCs, GSK-3484862-induced Dnmt1 requires accessory factor Uhrf1 its E3 ubiquitin ligase activity. We also hypomethylation induced compound reversible after removal. Together, results indicate this degrader/inhibitor will be valuable tool dissecting coordinated events linking gene expression identifying downstream effectors ultimately regulate response altered tissue/cell-specific manner.

Language: Английский

Citations

23
Epigenetic modulations in triple-negative breast cancer: Therapeutic implications for tumor microenvironment DOI Creative Commons
Linlin Zhou, Danny Yu

Pharmacological Research, Journal Year: 2024, Volume and Issue: 204, P. 107205 - 107205

Published: May 6, 2024

Triple-negative breast cancer (TNBC) is an aggressive subtype lacking estrogen receptors, progesterone receptors and lacks HER2 overexpression. This absence of critical molecular targets poses significant challenges for conventional therapies. Immunotherapy, remarkably immune checkpoint blockade, offers promise TNBC treatment, but its efficacy remains limited. Epigenetic dysregulation, including altered DNA methylation, histone modifications, imbalances in regulators such as BET proteins, plays a crucial role development resistance to treatment. Hypermethylation tumor suppressor gene promoters the imbalance methyltransferases EZH2 deacetylases (HDACs) profoundly influence cell proliferation, survival, metastasis. In addition, epigenetic alterations critically shape microenvironment (TME), composition, cytokine signaling, expression, ultimately contributing evasion. Targeting these mechanisms with specific inhibitors HDAC combination immunotherapy represents compelling strategy remodel TME, potentially overcoming evasion enhancing therapeutic outcomes TNBC. review aims comprehensively elucidate current understanding modulation TNBC, on potential combining therapies overcome posed by this subtype.

Language: Английский

Citations

15
Natural products reverse cancer multidrug resistance DOI Creative Commons
Jiayu Zou, Qilei Chen,

Xiao-Ci Luo

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: March 8, 2024

Cancer stands as a prominent global cause of death. One the key reasons why clinical tumor chemotherapy fails is multidrug resistance (MDR). In recent decades, accumulated studies have shown how Natural Product-Derived Compounds can reverse MDR. Discovering novel potential modulators to reduce MDR by has become popular research area across globe. Numerous mainly focus on natural products including flavonoids, alkaloids, terpenoids, polyphenols and coumarins for their modulatory activity. regulating signaling pathways or relevant expressed protein gene. Here we perform deep review previous achievements, advances in development treatment This aims provide some insights study products.

Language: Английский

Citations

14
Extracellular vesicles released by hypoxia‐induced tumor‐associated fibroblasts impart chemoresistance to breast cancer cells via long noncoding RNA H19 delivery DOI
Shuang Tao, Jian Wang, Fang Li

et al.

The FASEB Journal, Journal Year: 2024, Volume and Issue: 38(2)

Published: Jan. 10, 2024

Abstract Recently, extracellular vesicles (EVs) have been emphasized in regulating the hypoxic tumor microenvironment of breast cancer (BC), where tumor‐associated fibroblasts (TAFs) play a significant role. In this study, we describe possible molecular mechanisms behind pro‐tumoral effects EVs, secreted by hypoxia (HP)‐induced TAFs, on BC cell growth, metastasis, and chemoresistance. These are based long noncoding RNA H19 (H19) identified microarray analysis. We employed an silico approach to identify differentially expressed lncRNAs that were associated with BC. Subsequently, explored downstream regulatory mechanisms. isolated EVs from TAFs exposed HP, these denoted as HP‐TAF‐EVs henceforth. MTT, transwell, flow cytometry, TUNEL assays performed assess malignant phenotypes cells. A paclitaxel (TAX)‐resistant line was constructed, xenograft lung metastasis models established nude mice for vivo verification. Our observation revealed lncRNA significantly overexpressed, whereas miR‐497 notably downregulated HP induced activation stimulated secretion EVs. Coculture cells led increase TAX resistance latter. upregulated methylation delivering H19, which recruited DNMT1, thus lowering expression miR‐497. addition, H19‐containing hindered expression, enhancing tumorigenesis vivo. study presents evidence contribution reduction through recruitment turn promotes chemoresistance

Language: Английский

Citations

9
Unveiling DNA methylation: early diagnosis, risk assessment, and therapy for endometrial cancer DOI Creative Commons

Minzhen Li,

Zhili Xia,

Ruiyu Wang

et al.

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 14

Published: Jan. 20, 2025

Endometrial cancer (EC), one of the most common gynecologic malignancies worldwide, poses a significant burden particularly among young women, with poor treatment outcomes and prognosis for advanced recurrent patients. Epigenetic changes, encompassing DNA methylation, are involved in occurrence progression tumors hold promise as effective tools screening, early diagnosis, strategy, efficacy evaluation, analysis. This review provides comprehensive summary methylation-based diagnostic biomarkers EC, focus on recent valuable research findings published past two years. The discussion is organized according to sample sources, including cervical scraping, vaginal fluid, urine, blood, tissue. Additionally, we outline role methylation EC risk assessment, such carcinogenesis risk, feasibility fertility preservation approaches, overall prognosis, aiming provide personalized decisions Finally, researches resistance first-line development new drugs, envision future applications EC.

Language: Английский

Citations

1
DNA methylation and immune evasion in triple-negative breast cancer: challenges and therapeutic opportunities DOI Creative Commons

Wenyu Cai,

Xiaoli Cai,

Yi-ran Fei

et al.

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 15

Published: Feb. 6, 2025

Triple-negative breast cancer (TNBC) is an aggressive subtype of characterized by the lack estrogen receptor (ER), progesterone (PR), and human epidermal growth factor 2 (HER2). Chemotherapy remains primary treatment option, yet TNBC frequently develops resistance, leading to relapse metastasis. Emerging evidence highlights potential combining DNA methylation inhibitors with immune checkpoint (ICIs). contributes escape silencing immune-regulatory genes, thereby reducing tumor's visibility cells. Reversing this epigenetic modification can reinvigorate surveillance enhance efficacy immunotherapies. This review discusses role in progression evasion, focusing on recent advances combination therapies involving ICIs. We discuss underlying mechanisms that enable these therapeutic synergies, preclinical clinical supporting approach, challenges posed tumor heterogeneity, drug toxicity. Finally, we explore for personalized strategies incorporating multi-omics data optimize outcomes. The integration immunotherapy offers a promising avenue improving survival patients.

Language: Английский

Citations

1
c-Myc knockdown restores tamoxifen sensitivity in triple-negative breast cancer by reactivating the expression of ERα: the central role of miR-152 and miR-148a DOI
Chao Dong,

Yonghong Sun,

Xiaoli Xu

et al.

Breast Cancer, Journal Year: 2025, Volume and Issue: unknown

Published: March 3, 2025

Language: Английский

Citations

1
Blood-based DNA methylation signatures in cancer: A systematic review DOI Creative Commons
Yongzheng Li, Zhiyao Fan,

Yufan Meng

et al.

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2022, Volume and Issue: 1869(1), P. 166583 - 166583

Published: Oct. 18, 2022

Language: Английский

Citations

36