Recent advances in HER2 positive breast cancer epigenetics: Susceptibility and therapeutic strategies

HER2 amplification/overexpression accounts for aggressive clinical features of HER2 positive breast cancer. Epigenetic changes including DNA methylation, histone modifications and ncRNAs/miRNAs are associated with regulation of DNA chromatin and specifically, gene transcription. Hence, these produce...

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Bibliographic Details
Published in:European journal of medicinal chemistry 2017-12, Vol.142, p.316-327
Main Authors: Singla, Heena, Ludhiadch, Abhilash, Kaur, Raman Preet, Chander, Harish, Kumar, Vinod, Munshi, Anjana
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents, Immunological - pharmacology
Antineoplastic Agents, Immunological - therapeutic use
Breast - drug effects
Breast - metabolism
Breast - pathology
Breast Neoplasms - drug therapy
Breast Neoplasms - genetics
Breast Neoplasms - pathology
DNA Methylation
Epigenesis, Genetic
Female
Gene Expression Regulation, Neoplastic
HER2 positive breast cancer
Histone modifications
Humans
miRNA
Molecular Targeted Therapy
ncRNA
Protein Kinase Inhibitors - pharmacology
Protein Kinase Inhibitors - therapeutic use
Quinazolines - pharmacology
Quinazolines - therapeutic use
Receptor, ErbB-2 - antagonists & inhibitors
Receptor, ErbB-2 - genetics
Susceptibility
Therapy
Trastuzumab - pharmacology
Trastuzumab - therapeutic use
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Summary:HER2 amplification/overexpression accounts for aggressive clinical features of HER2 positive breast cancer. Epigenetic changes including DNA methylation, histone modifications and ncRNAs/miRNAs are associated with regulation of DNA chromatin and specifically, gene transcription. Hence, these produce eminent effects upon proto-oncogenes, tumor-suppressors and key cancer-regulatory signaling pathways. Understanding of epigenomic regulation of HER2 overexpression and signaling may help uncover the unmatchable physiology of HER2 gene/protein. Moreover, this may also aid in resolving the major issue of resistance-development towards HER2 targeted agents (trastuzumab and lapatinib), since epigenetic alterations are important therapeutic markers and modulate the response towards HER2 targeted therapy. Therefore, in this review the information regarding various epigenetic markers implicated in HER2 positive breast cancer susceptibility and therapeutic-strategies has been compiled. [Display omitted] •HER2 overexpression/amplification is key marker in breast cancer.•Epigenetic modulations regulate HER2 gene chromatin.•These have impact on HER2-induced signaling.•They also alter the response towards HER2-targeted therapy.
ISSN:0223-5234
1768-3254
DOI:10.1016/j.ejmech.2017.07.075