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

摘要

Abstract 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. Graphical abstract Display Omitted Highlights ? 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.