Hydralazine–valproate: a repositioned drug combination for the epigenetic therapy of cancer

Dueñas‐González, Alfonso; Coronel, Jaime; Cetina, Lucely; González-Fierro, Aurora; Chávez‐Blanco, Alma; Taja‐Chayeb, Lucía

doi:10.1517/17425255.2014.947263

Cited by 53 publications

(17 citation statements)

References 68 publications

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“…These novel drugs show higher potency and specificity targeting other enzymes, including bromodomain and extra terminal protein (BET), lysine-specific demethylase 1A (LSD1/KDM1A), mutant isocitrate dehydrogenase (IDH), histone methyltransferase (HMT) and protein arginine methyltransferase (PRMT). A recent but promising trend in the cancer treatment landscape is combination therapies of epigenetic drugs with other compounds ( Dueñas-Gonzalez et al, 2014 ; Ahuja et al, 2016 ; Raynal et al, 2017 ). Epigenetic inhibitors could be the lead to treat multiple disease types apart from cancer.…”

Section: Interventions and Future Aspectsmentioning

confidence: 99%

Epigenetics and Metabolism in Health and Disease

Tzika¹,

Dreker²,

Imhof

2018

Front. Genet.

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In the next 10 years, one billion people are estimated to suffer from disabling consequences of metabolic disorders, making them the number one noncommunicable disease on a global scale by 2030. Lots of risk factors such as dietary intake, lack of exercise and other life style behaviors are considered to play a role in the development of metabolic disorders. Despite the efforts that have been undertaken to unravel their potential causes, the underlying molecular mechanisms remain elusive. Evidence suggests that the pathogenesis involves changes on chromatin and chromatin-modifying enzymes, which can contribute to a persistent dysregulated metabolic phenotype. Indeed, a rising number of studies links epigenetic alterations with the diagnosis and prognosis of metabolic disorders. A prerequisite for exploiting these findings for pharmacological intervention is a detailed understanding of how differential epigenetic modifications control cell metabolism. In this mini review, we summarize the recent advances in uncovering the interplay between epigenetics and metabolic pathways on a cellular level and highlight potential new avenues for alternative treatment strategies.

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Section: Interventions and Future Aspectsmentioning

confidence: 99%

Epigenetics and Metabolism in Health and Disease

Tzika¹,

Dreker²,

Imhof

2018

Front. Genet.

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“…Studies conducted with ESCC and esophageal adenocarcinoma (EAC) cells, in vitro as well as in human esophageal carcinomas, demonstrated decreased cell migration. Furthermore, the combination of the DNMT inhibitor hydralazine-valproate and an HDAC inhibitor were applied for the treatment of CTCL [103]. The phase I trial confirmed safe drug administration, although additional studies are required to demonstrate efficacy.…”

Section: Cancer and Epigeneticsmentioning

confidence: 96%

Nutrition, Cancer Genetics and Epigenetics

Lundström¹

2019

obm genet

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Epidemiological data and meta-analysis have confirmed that there exists a strong association between nutrition and disease risk. In the context of cancer, it has been demonstrated that unhealthy diets increase the risk of disease. On the other hand, major dietary interventions and lifestyle changes have been demonstrated to provide therapeutic efficacy in cancer patients. Genetic mechanisms have been reported to be associated with cancer development induced by environmental and nutritional factors. Genetics plays an important role in the designing of personalized drugs and diets. Epigenetics has also been demonstrated to be affected by nutrition, leading to increased risk of disease when unhealthy diets are consumed, while healthy nutrition is able to provide both prophylactic and therapeutic efficacy.

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“…The mechanism of action of hydrazaline is still a controversial issue as some groups claimed that it binds to the catalytic site of DNMT, while others reported that it reduces DNMT1 and DNMT3a expression via the extracellular signal–regulated kinase (ERK) pathway inhibition [132,133]. This drug is in different phases of clinical trials as an anticancer drug, and registered in Mexico in combination with an HDAC inhibitor, i.e., magnesium valproate, for MDS treatment [134,135]. …”

Section: Inhibition Of Dna Methylation: Other Approachesmentioning

confidence: 99%

DNA Methylation Targeting: The DNMT/HMT Crosstalk Challenge

et al. 2017

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Chromatin can adopt a decondensed state linked to gene transcription (euchromatin) and a condensed state linked to transcriptional repression (heterochromatin). These states are controlled by epigenetic modulators that are active on either the DNA or the histones and are tightly associated to each other. Methylation of both DNA and histones is involved in either the activation or silencing of genes and their crosstalk. Since DNA/histone methylation patterns are altered in cancers, molecules that target these modifications are interesting therapeutic tools. We present herein a vast panel of DNA methyltransferase inhibitors classified according to their mechanism, as well as selected histone methyltransferase inhibitors sharing a common mode of action.

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Hydralazine–valproate: a repositioned drug combination for the epigenetic therapy of cancer

Cited by 53 publications

References 68 publications

Epigenetics and Metabolism in Health and Disease

Epigenetics and Metabolism in Health and Disease

Nutrition, Cancer Genetics and Epigenetics

DNA Methylation Targeting: The DNMT/HMT Crosstalk Challenge

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