Pharmacological Advancements of PRC2 in Cancer Therapy: A Narrative Review DOI Creative Commons

Michael S. Wang,

Jonathan H. Sussman,

Jun-Jun Xu

и другие.

Life, Год журнала: 2024, Номер 14(12), С. 1645 - 1645

Опубликована: Дек. 11, 2024

Polycomb repressive complex 2 (PRC2) is known to regulate gene expression and chromatin structure as it methylates H3K27, resulting in silencing. Studies have shown that PRC2 has dual functions oncogenesis allow function both an oncogene a tumor suppressor. Because of this, nuanced strategies are necessary promote or inhibit activity therapeutically. Given the therapeutic vulnerabilities associated risks oncological applications, structured literature review on was conducted showcase similar cofactor competitor inhibitors PRC2. Key such Tazemetostat, GSK126, Valemetostat, UNC1999 promise for clinical use within various studies. Tazemetostat GSK126 highly selective wild-type lymphoma-associated EZH2 mutants. Valemetostat orally bioavailable SAM-competitive EZH1 EZH2, giving them greater efficacy against potential drug resistance. The development other inhibitors, particularly targeting EED SUZ12 subunit, also being explored with drugs like 226. This aims bridge gaps current provide unified perspective promising agents treatment lymphomas solid tumors.

Язык: Английский

Cellular Epigenetic Targets and Epidrugs in Breast Cancer Therapy: Mechanisms, Challenges, and Future Perspectives DOI Creative Commons

Ibrahim S. Alalhareth,

Saleh M. Alyami,

Abdulrhman Alshareef

и другие.

Pharmaceuticals, Год журнала: 2025, Номер 18(2), С. 207 - 207

Опубликована: Фев. 3, 2025

Breast cancer is the most common malignancy affecting women, manifesting as a heterogeneous disease with diverse molecular characteristics and clinical presentations. Recent studies have elucidated role of epigenetic modifications in pathogenesis breast cancer, including drug resistance efflux characteristics, offering potential new diagnostic prognostic markers, treatment efficacy predictors, therapeutic agents. Key include DNA cytosine methylation covalent modification histone proteins. Unlike genetic mutations, reprogramming landscape epigenome promising targeted therapy for reversal resistance. Epidrugs, which target modifications, can provide novel options by reversing acquired to treatment. Currently, approach involves combination therapies consisting epidrugs immune checkpoint inhibitors. This review examines aberrant regulation initiation progression, focusing on related estrogen signaling, resistance, epithelial–mesenchymal transition (EMT). It existing drugs treating agents that modify DNA, inhibitors acetyltransferases, deacetylases, methyltransferases, demethyltransferases. also delves into ongoing combining other addresses upcoming obstacles this field.

Язык: Английский

Процитировано

0
Gene expression associated with endocrine therapy resistance in estrogen receptor-positive breast cancer DOI Creative Commons
Veronica Jones,

Hongwei Yin,

Yuan Yuan

и другие.

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Фев. 28, 2025

Despite endocrine therapy (ET), approximately 20–40% of Stage I–III estrogen receptor-positive breast cancer (ER + BC) patients experience recurrence. Recurrence while on ET is indicative resistance. This study aimed to identify differentially expressed genes (DEGs) associated with recurrence during (ET resistance) and explore gene expression differences across PAM50 molecular subtypes. Eighty tumor specimens from 79 treated at the City Hope Comprehensive Cancer Center (2012–2016) were analyzed using NanoString technology. Fourteen (17.7%) experienced over a median follow-up 68 months (range 35–104 months). Key upregulated DEGs in group included EZH2 (log2 fold change[log2FC]: 0.67, p = 0.0017), WNT11 (log2FC: 1.08, 0.0088), ITGB6 0.80, 0.0312), TOP2A 0.79, 0.0381). Downregulated SNAI2 − 0.63, 0.0055), ITPR1 0.75, 0.0083), CD10 0.70, 0.0092), PTEN 0.29, 0.0163), VRD 0.46, 0.0184), WNT5A 0.76, 0.0272). positively correlated proliferation scores, emerged as potential biomarkers independently These findings suggest novel biomarker candidates that could help overcome resistance, reduce recurrence, improve outcomes ER BC.

Язык: Английский

Процитировано

0
Bisphenol S (BPS) induces glioblastoma progression via regulation of EZH2-mediated PI3K/AKT/mTOR pathway in U87-MG cells DOI Creative Commons

Moon Yi Ko,

Heejin Park, Younhee Kim

и другие.

Toxicology, Год журнала: 2024, Номер 507, С. 153898 - 153898

Опубликована: Июль 18, 2024

Bisphenol S (BPS), an alternative to bisphenol A (BPA), exerts proliferative effects similar those of BPA. BPS is a representative endocrine disruptor associated with cancer progression. However, the mechanisms underlying BPS-induced glioblastoma progression are not fully understood. To investigate on glioblastoma, U-87 MG cell lines were exposed BPS. The study focused analyzing proliferation and migration cells. Furthermore, involvement enhancer zeste homolog 2 (EZH2)-mediated phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target rapamycin (mTOR) pathway was examined. Pharmacological approaches employed inhibit EZH2 activity observe its changes. results indicated that promoted cells at concentration 0.1 µM. These changes appeared be linked activation EZH2-mediated PI3K/AKT/mTOR pathway. Moreover, inhibiting using pharmacological restored BPS-mediated induction migration. In conclusion, this induces through upregulation. Therefore, targeting could considered potential therapeutic strategy for treatment glioblastoma.

Язык: Английский

Процитировано

1
EZH2 mutation is associated with the development of visceral metastasis by enhancing proliferation and invasion and inhibiting apoptosis in breast cancer cells DOI Creative Commons
Fan Wu, Nani Li, Xiufeng Wu

и другие.

BMC Cancer, Год журнала: 2024, Номер 24(1)

Опубликована: Сен. 19, 2024

Язык: Английский

Процитировано

1
Unraveling non-coding RNAs in breast cancer: mechanistic insights and therapeutic potential DOI Creative Commons
Muqtada Shaikh, Gaurav Doshi

Medical Oncology, Год журнала: 2024, Номер 42(1)

Опубликована: Дек. 27, 2024

Язык: Английский

Процитировано

1
Identification of Poliovirus Receptor-like 3 Protein as a Prognostic Factor in Triple-Negative Breast Cancer DOI Creative Commons
Gian Marco Leone, Katia Mangano, S Caponnetto

и другие.

Cells, Год журнала: 2024, Номер 13(15), С. 1299 - 1299

Опубликована: Авг. 3, 2024

Triple-negative breast cancer (TNBC) represents an aggressive subtype of cancer, with a bad prognosis and lack targeted therapeutic options. Characterized by the absence estrogen receptors, progesterone HER2 expression, TNBC is often associated significantly lower survival rate compared to other subtypes. Our study aimed explore prognostic significance 83 immune-related genes, using transcriptomic data from TCGA database. analysis identified Poliovirus Receptor-Like 3 protein (PVRL3) as critical negative marker in patients. Furthermore, we found that Enhancer Zeste Homolog 2 (EZH2), well-known epigenetic regulator, plays pivotal role modulating PVRL3 levels cell lines expressing EZH2 along high PVRL3. The elucidation EZH2-PVRL3 regulatory axis provides valuable insights into molecular mechanisms underlying aggressiveness opens up potential pathways for personalized intervention.

Язык: Английский

Процитировано

0
Therapeutic targeting potential of the protein lysine and arginine methyltransferases to reverse cancer chemoresistance DOI Creative Commons
Isaac Micallef,

Kimberly Fenech,

Byron Baron

и другие.

Frontiers in Molecular Biosciences, Год журнала: 2024, Номер 11

Опубликована: Дек. 5, 2024

Cancer treatments have continued to improve tremendously over the past decade, but therapy resistance is still a common, major factor encountered by patients diagnosed with cancer. Chemoresistance arises due various circumstances and among these causes, increasing evidence has shown that enzymes referred as protein methyltransferases (PMTs) play significant role in development of chemoresistance cancers. These are responsible for methylation different amino acids, particularly lysine arginine, via (PKMTs) arginine (PRMTs), respectively. Various PMTs been identified be dysregulated cancer chemoresistance. Nonetheless, functional poorly characterised. This advocates need innovative approaches technologies suitable better characterisation their potential clinical inhibitors. In case handful PMTs, inhibitory small molecules which can function anticancer drugs developed also entered trials. Considering all this, become promising valuable target related research. review will give introduction on PKMTs PRMTs families cancers known proteins targeted respective enzymes. The focus then shift towards involved inhibitors against these, together mode action. Lastly, current obstacles future perspectives PMT discussed.

Язык: Английский

Процитировано

0
Pharmacological Advancements of PRC2 in Cancer Therapy: A Narrative Review DOI Creative Commons

Michael S. Wang,

Jonathan H. Sussman,

Jun-Jun Xu

и другие.

Life, Год журнала: 2024, Номер 14(12), С. 1645 - 1645

Опубликована: Дек. 11, 2024

Polycomb repressive complex 2 (PRC2) is known to regulate gene expression and chromatin structure as it methylates H3K27, resulting in silencing. Studies have shown that PRC2 has dual functions oncogenesis allow function both an oncogene a tumor suppressor. Because of this, nuanced strategies are necessary promote or inhibit activity therapeutically. Given the therapeutic vulnerabilities associated risks oncological applications, structured literature review on was conducted showcase similar cofactor competitor inhibitors PRC2. Key such Tazemetostat, GSK126, Valemetostat, UNC1999 promise for clinical use within various studies. Tazemetostat GSK126 highly selective wild-type lymphoma-associated EZH2 mutants. Valemetostat orally bioavailable SAM-competitive EZH1 EZH2, giving them greater efficacy against potential drug resistance. The development other inhibitors, particularly targeting EED SUZ12 subunit, also being explored with drugs like 226. This aims bridge gaps current provide unified perspective promising agents treatment lymphomas solid tumors.

Язык: Английский

Процитировано

0