Epigenetic Modulators as Therapeutic Agents in Cancer DOI Open Access

Eshaan Patnaik,

Chikezie O. Madu, Yi Lü

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(19), P. 14964 - 14964

Published: Oct. 6, 2023

Epigenetics play a crucial role in gene regulation and cellular processes. Most importantly, its dysregulation can contribute to the development of tumors. Epigenetic modifications, such as DNA methylation histone acetylation, are reversible processes that be utilized targets for therapeutic intervention. inhibitors disrupt patterns by inhibiting methyltransferases. Such restore normal expression patterns, they effective against various forms cancer. Histone deacetylase increase acetylation levels, leading altered expressions. Like inhibitors, methyltransferase target molecules involved methylation. Bromodomain extra-terminal domain proteins expression. They oncogene inducing anti-proliferative effects seen Understanding epigenetic modifications utilizing will offer new possibilities cancer research.

Language: Английский

The language of chromatin modification in human cancers DOI
Shuai Zhao, C. David Allis, Gang Greg Wang

et al.

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

Published: May 17, 2021

Language: Английский

Citations

302
Epigenetics and beyond: targeting writers of protein lysine methylation to treat disease DOI
Kamakoti P. Bhat, H. Ümit Kanıskan, Jian Jin

et al.

Nature Reviews Drug Discovery, Journal Year: 2021, Volume and Issue: 20(4), P. 265 - 286

Published: Jan. 19, 2021

Language: Английский

Citations

180
The role of histone modifications: from neurodevelopment to neurodiseases DOI Creative Commons
Jisu Park, Kyubin Lee, Kyunghwan Kim

et al.

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

Published: July 6, 2022

Abstract Epigenetic regulatory mechanisms, including DNA methylation, histone modification, chromatin remodeling, and microRNA expression, play critical roles in cell differentiation organ development through spatial temporal gene regulation. Neurogenesis is a sophisticated complex process by which neural stem cells differentiate into specialized brain types at specific times regions of the brain. A growing body evidence suggests that epigenetic such as modifications, allow fine-tuning coordination spatiotemporal expressions during neurogenesis. Aberrant modifications contribute to neurodegenerative neuropsychiatric diseases. Herein, recent progress understanding regulating embryonic adult neurogenesis comprehensively reviewed. The implicated diseases are also covered, future directions this area provided.

Language: Английский

Citations

165
Elevated NSD3 histone methylation activity drives squamous cell lung cancer DOI
Gang Yuan, Natasha Flores, Simone Hausmann

et al.

Nature, Journal Year: 2021, Volume and Issue: 590(7846), P. 504 - 508

Published: Feb. 3, 2021

Language: Английский

Citations

118
Histone editing elucidates the functional roles of H3K27 methylation and acetylation in mammals DOI
Aditya Sankar,

Faizaan Mohammad,

Arun Kumar Sundaramurthy

et al.

Nature Genetics, Journal Year: 2022, Volume and Issue: 54(6), P. 754 - 760

Published: June 1, 2022

Language: Английский

Citations

109
Targeting protein modifications in metabolic diseases: molecular mechanisms and targeted therapies DOI Creative Commons
Xiumei Wu, Mengyun Xu,

M. Geng

et al.

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

Published: May 27, 2023

The ever-increasing prevalence of noncommunicable diseases (NCDs) represents a major public health burden worldwide. most common form NCD is metabolic diseases, which affect people all ages and usually manifest their pathobiology through life-threatening cardiovascular complications. A comprehensive understanding the will generate novel targets for improved therapies across spectrum. Protein posttranslational modification (PTM) an important term that refers to biochemical specific amino acid residues in target proteins, immensely increases functional diversity proteome. range PTMs includes phosphorylation, acetylation, methylation, ubiquitination, SUMOylation, neddylation, glycosylation, palmitoylation, myristoylation, prenylation, cholesterylation, glutathionylation, S-nitrosylation, sulfhydration, citrullination, ADP ribosylation, several PTMs. Here, we offer review roles pathological consequences, including diabetes, obesity, fatty liver hyperlipidemia, atherosclerosis. Building upon this framework, afford description proteins pathways involved by focusing on PTM-based protein modifications, showcase pharmaceutical intervention preclinical studies clinical trials, future perspectives. Fundamental research defining mechanisms whereby regulate open new avenues therapeutic intervention.

Language: Английский

Citations

107
Cancer epigenetics: from laboratory studies and clinical trials to precision medicine DOI Creative Commons
Xinyang Yu, Hao Zhao, Ruiqi Wang

et al.

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: Jan. 15, 2024

Abstract Epigenetic dysregulation is a common feature of myriad human diseases, particularly cancer. Defining the epigenetic defects associated with malignant tumors has become focus cancer research resulting in gradual elucidation cell regulation. In fact, most stages tumor progression, including tumorigenesis, promotion, and recurrence are accompanied by alterations, some which can be reversed drugs. The main objective therapy era personalized precision medicine to detect biomarkers improve risk assessment, diagnosis, targeted treatment interventions. Rapid technological advancements streamlining characterization molecular changes cancers have propelled drug development. This review summarizes mechanisms discusses past present examples inhibitors diagnosis treatment, an emphasis on development enzyme or final part, prospect precise considered based better understanding abnormalities

Language: Английский

Citations

100
Signaling pathways and targeted therapies in lung squamous cell carcinoma: mechanisms and clinical trials DOI Creative Commons

Zhenyi Niu,

Runsen Jin,

Yan Zhang

et al.

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

Published: Oct. 5, 2022

Lung cancer is the leading cause of cancer-related death across world. Unlike lung adenocarcinoma, patients with squamous cell carcinoma (LSCC) have not benefitted from targeted therapies. Although immunotherapy has significantly improved patients' outcomes, relatively low response rate and severe adverse events hinder clinical application this promising treatment in LSCC. Therefore, it vital importance to a better understanding mechanisms underlying pathogenesis LSCC as well inner connection among different signaling pathways, which will surely provide opportunities for more effective therapeutic interventions In review, new insights were given about classical pathways been proved other types but LSCC, including PI3K pathway, VEGF/VEGFR signaling, CDK4/6 pathway. Other may potentials also discussed, FGFR1 EGFR KEAP1/NRF2 Next, chromosome 3q, harbors two key differentiation markers SOX2 TP63 discussed its related potential targets. We provided some progress epigenetic therapies immune checkpoints blockade (ICB) Subsequently, we outlined combination strategies ICB Finally, prospects challenges exploration novel

Language: Английский

Citations

99
Epigenetic mechanisms of Immune remodeling in sepsis: targeting histone modification DOI Creative Commons
Dan Wu,

Yuxin Shi,

Hao Zhang

et al.

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(2)

Published: Feb. 11, 2023

Abstract Sepsis is a life-threatening disorder disease defined as infection-induced dysregulated immune responses and multiple organ dysfunction. The imbalance between hyperinflammation immunosuppression crucial feature of sepsis immunity. Epigenetic modifications, including histone DNA methylation, chromatin remodeling, non-coding RNA, play essential roles in regulating immunity through epi-information independent the sequence. In recent years, mechanisms modification have received increasing attention, with ongoing discoveries novel types modifications. Due to capacity for prolonged effects on cells, modifications can induce cell reprogramming participate long-term immunosuppressed state sepsis. Herein, we systematically review current involved regulation sepsis, summarize their role from an perspective provide potential therapeutic opportunities targeting treatment.

Language: Английский

Citations

56
Epigenetics-targeted drugs: current paradigms and future challenges DOI Creative Commons

Wanlin Dai,

Xinbo Qiao, Yuanyuan Fang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Nov. 26, 2024

Epigenetics governs a chromatin state regulatory system through five key mechanisms: DNA modification, histone RNA remodeling, and non-coding regulation. These mechanisms their associated enzymes convey genetic information independently of base sequences, playing essential roles in organismal development homeostasis. Conversely, disruptions epigenetic landscapes critically influence the pathogenesis various human diseases. This understanding has laid robust theoretical groundwork for developing drugs that target epigenetics-modifying pathological conditions. Over past two decades, growing array small molecule targeting such as methyltransferase, deacetylase, isocitrate dehydrogenase, enhancer zeste homolog 2, have been thoroughly investigated implemented therapeutic options, particularly oncology. Additionally, numerous epigenetics-targeted are undergoing clinical trials, offering promising prospects benefits. review delineates epigenetics physiological contexts underscores pioneering studies on discovery implementation drugs. include inhibitors, agonists, degraders, multitarget agents, aiming to identify practical challenges avenues future research. Ultimately, this aims deepen epigenetics-oriented strategies further application settings.

Language: Английский

Citations

34