The future of epigenetic therapy in solid tumours--lessons from the past.
TLDR
It is hypothesized that in using low-dose epigenetic-modulating agents, tumour cells can be reprogrammed, which overrides any immediate cytotoxic and off-target effect observed at high dose, and could give these agents a prominent place in cancer management.Abstract:
The promise of targeting epigenetic abnormalities for cancer therapy has not been realized for solid tumours, although increasing evidence is demonstrating its worth in haematological malignancies. In fact, true clinical efficacy in haematopoietic-related neoplasms has only become evident at low doses of epigenetic-targeting drugs (namely, inhibitors of histone deacetylase and DNA methyltransferases). Describing data from preclinical studies and early clinical trial results, we hypothesize that in using low-dose epigenetic-modulating agents, tumour cells can be reprogrammed, which overrides any immediate cytotoxic and off-target effect observed at high dose. We suggest that such optimization of drug dosing and scheduling of currently available agents could give these agents a prominent place in cancer management--when used alone or in combination with other therapies. If so, optimal use of these known agents might also pave the way for the introduction of other agents that target the epigenome.read more
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Development of a versatile DNMT and HDAC inhibitor C02S modulating multiple cancer hallmarks for breast cancer therapy.
Zigao Yuan,Shaopeng Chen,Chunmei Gao,Qiuzi Dai,Cunlong Zhang,Qinsheng Sun,Jin-Shun Lin,Chun Guo,Yu Zong Chen,Yuyang Jiang,Yuyang Jiang +10 more
TL;DR: The development of a novel dual DNMT and HDAC inhibitor C02S which showed potent enzymatic inhibitory activities against DNMT1, DNMT3A,DNMT3B andHDAC1 with IC50 values of 2.05, 0.93, 1.16 µM, respectively is reported.
Journal ArticleDOI
Development and validation of a CIMP-associated prognostic model for hepatocellular carcinoma
Ganxun Li,Weiqi Xu,Lu Zhang,Tongtong Liu,Guannan Jin,Jia Song,Jing-jing Wu,Yuwei Wang,Wei-xun Chen,Chuanhan Zhang,Xiaoping Chen,Zeyang Ding,Peng Zhu,Bixiang Zhang +13 more
TL;DR: This work highlights the potential clinical application value of CPM in predicting the overall survival of HCC patients and the mechanisms underlying the role of CIMP in hepatocarcinogenesis.
Journal ArticleDOI
Differential expression of histone deacetylase and acetyltransferase genes in gastric cancer and their modulation by trichostatin A
Fernanda Wisnieski,Danielle Queiroz Calcagno,Danielle Queiroz Calcagno,Mariana Ferreira Leal,Elizabeth Suchi Chen,Carolina Oliveira Gigek,Leonardo Caires Santos,Thaís Brilhante Pontes,Lucas Trevizani Rasmussen,Spencer Luiz Marques Payão,Paulo Pimentel Assumpção,Laércio Gomes Lourenço,Sâmia Demachki,Ricardo Artigiani,Rommel Rodríguez Burbano,Marilia Arruda Cardoso Smith +15 more
TL;DR: Assessment of messenger RNA levels of three histone deacetylases, two histone acetyltransferases, and two possible targets of these histone modifiers suggest that alteration of histone modifier genes play an important role in gastric carcinogenesis, contributing to MYC and CDKN1A deregulation.
Journal ArticleDOI
Role of Methylation in Pro- and Anti-Cancer Immunity.
TL;DR: In this article, the role of DNA and RNA methylation in myeloid and lymphoid cells in the activation, differentiation, and function that control the innate and adaptive immune responses in cancer and non-cancer contexts.
Journal ArticleDOI
Therapeutic Targets for Adrenocortical Carcinoma in the Genomics Era.
TL;DR: It is revealed that ACC consists of three distinct molecular subtypes with divergent clinical outcomes and implicates differential regulation of Wnt signaling, cell cycle, DNA methylation, immune biology, and steroidogenesis in ACC biology.
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