The role of histone deacetylase inhibitors in metastatic breast cancer

Zucchetti, B; Shimada, Andrea Kazumi; Katz, Artur; Curigliano, Giuseppe

doi:10.1016/j.breast.2018.12.001

Cited by 51 publications

(34 citation statements)

References 30 publications

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“…Histone acetylation is also a PTM that is found to have wide role in transcriptional regulation of gene [137,138]. Acetylation is the outcome of balance between writer histone acetyl transferase (HAT) and eraser histone deacetylase (HDAC) molecule [139]. HAT activity is associated with open chromatin structure owing to its donation of acetyl group to the histone tail while HDAC reverses the action of HAT activity and leads to the closed conformation of the chromatin structure.…”

Section: B Acetylationmentioning

confidence: 99%

A three layered histone epigenetics in breast cancer metastasis

2020

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Thanks to the advancement in science and technology and a significant number of cancer research programs being carried out throughout the world, the prevention, prognosis and treatment of breast cancer are improving with a positive and steady pace. However, a stern thoughtful attention is required for the metastatic breast cancer casesthe deadliest of all types of breast cancer, with a character of relapse even when treated. In an effort to explore the less travelled avenues, we summarize here studies underlying the aspects of histone epigenetics in breast cancer metastasis. Authoritative reviews on breast cancer epigenetics are already available; however, there is an urgent need to focus on the epigenetics involved in metastatic character of this cancer. Here we put forward a comprehensive review on how different layers of histone epigenetics comprising of histone chaperones, histone variants and histone modifications interplay to create breast cancer metastasis landscape. Finally, we propose a hypothesis of integrating histone-epigenetic factors as biomarkers that encompass different breast cancer subtypes and hence could be exploited as a target of larger population.

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Section: B Acetylationmentioning

confidence: 99%

A three layered histone epigenetics in breast cancer metastasis

2020

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“…It is worth noting that HDACs have become important therapeutic targets in various cancer with the increasing number of reports on the HDAC inhibitors (HDACi). There are currently 5 HDAC drugs on the market (Zucchetti et al, 2019). Four HDAC inhibitors were approved by the US FDA for the clinical treatment of peripheral T-cell lymphoma, cutaneous T-cell lymphoma and multiple myeloma, and one was approved by the China Food and Drug Administration for peripheral T-cell lymphoma.…”

Section: Insight Into the Histone Acetylationmentioning

confidence: 99%

“…However, epigenetic changes mostly are demonstrated to be blamed for the cause of breast cancer progression based on the literature in the last two decades (Shukla et al, 2019). In addition to the mutations in the tumor-suppressor genes or the proto-oncogenes induced breast cancer progression, epigenetic aberrations also increase the events of breast metastasis (Chatterjee et al, 2018;Zucchetti et al, 2019). The accumulation of epigenetic changes in the tumor-related genes may contribute to the "cancer epigenome" in the alteration of gene expression without changes in the DNA sequence.…”

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confidence: 99%

Perspectives on the Role of Histone Modification in Breast Cancer Progression and the Advanced Technological Tools to Study Epigenetic Determinants of Metastasis

et al. 2020

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Metastasis is a complex process that involved in various genetic and epigenetic alterations during the progression of breast cancer. Recent evidences have indicated that the mutation in the genome sequence may not be the key factor for increasing metastatic potential. Epigenetic changes were revealed to be important for metastatic phenotypes transition with the development in understanding the epigenetic basis of breast cancer. Herein, we aim to present the potential epigenetic drivers that induce dysregulation of genes related to breast tumor growth and metastasis, with a particular focus on histone modification including histone acetylation and methylation. The pervasive role of major histone modification enzymes in cancer metastasis such as histone acetyltransferases (HAT), histone deacetylases (HDACs), DNA methyltransferases (DNMTs), and so on are demonstrated and further discussed. In addition, we summarize the recent advances of next-generation sequencing technologies and microfluidic-based devices for enhancing the study of epigenomic landscapes of breast cancer. This feature also introduces several important biotechnologists for identifying robust epigenetic biomarkers and enabling the translation of epigenetic analyses to the clinic. In summary, a comprehensive understanding of epigenetic determinants in metastasis will offer new insights of breast cancer progression and can be achieved in the near future with the development of innovative epigenomic mapping tools.

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“…By removing acetyl groups, HDACs reverse chromatin acetylation and alter transcription of oncogenes and tumor suppressor genes. 105,106 Therefore, the use of deep sampling approaches combined with Connectivity Map technologies (CMAP) allows fast finding of possible compounds and the design of new drugs that maximize the mechanisms of action needed to counteract the progression of the disease. The results obtained in this case study back the introduction of AI in Precision Medicine, since the drugs obtained are also currently being tested in TNBC.…”

Section: Trichostatin a (Tsa) Is A Potent And Specific Inhibitormentioning

confidence: 99%

<p>On the Role of Artificial Intelligence in Genomics to Enhance Precision Medicine</p>

Álvarez-Machancoses¹,

deAndrés-Galiana²,

Cernea³

et al. 2020

PGPM

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The complexity of orphan diseases, which are those that do not have an effective treatment, together with the high dimensionality of the genetic data used for their analysis and the high degree of uncertainty in the understanding of the mechanisms and genetic pathways which are involved in their development, motivate the use of advanced techniques of artificial intelligence and in-depth knowledge of molecular biology, which is crucial in order to find plausible solutions in drug design, including drug repositioning. Particularly, we show that the use of robust deep sampling methodologies of the altered genetics serves to obtain meaningful results and dramatically decreases the cost of research and development in drug design, influencing very positively the use of precision medicine and the outcomes in patients. The target-centric approach and the use of strong prior hypotheses that are not matched against reality (disease genetic data) are undoubtedly the cause of the high number of drug design failures and attrition rates. Sampling and prediction under uncertain conditions cannot be avoided in the development of precision medicine.

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The role of histone deacetylase inhibitors in metastatic breast cancer

Cited by 51 publications

References 30 publications

A three layered histone epigenetics in breast cancer metastasis

A three layered histone epigenetics in breast cancer metastasis

Perspectives on the Role of Histone Modification in Breast Cancer Progression and the Advanced Technological Tools to Study Epigenetic Determinants of Metastasis

<p>On the Role of Artificial Intelligence in Genomics to Enhance Precision Medicine</p>

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