INTERNATIONAL CONGRESS OF
PharmacoGenetics
Investigation of EZH2 Inhibitors and Epigenetic Alterations in the Development of Tamoxifen Resistance in Breast Cancer
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Farzaneh Ramezani Hombari ,1,*
1. Shahid Beheshti University of Medical Sciences, Health Park, Hakimieh, Second West Floor (Genomics Laboratory)
- Introduction: Breast cancer is the most common malignancy worldwide. Tamoxifen is the main hormonal therapy for oestrogen receptor (ER+) positive cases and plays a key role in inducing changes through H3K27me3 mechanisms and HER2/AKT pathway regulation. Increased expression of EZH2 in breast cancer is associated with tumour progression, metastasis, and treatment resistance. This study aims to systematically investigate the mechanisms of genetic resistance to tamoxifen using EZH2, and to evaluate this enzyme's potential therapeutic abilities using bioinformatics methods.
- Methods: Our studies in this area are based on previous bioinformatics studies. We based our study on bioinformatics databases and epigenetic changes, particularly the overactivity of the EZH2 enzyme (PRC2 complex selection), through expression mechanisms related to H3K27me3 methylation and the regulation of the HER2/AKT/mTOR pathways in establishing this key role. We conducted our studies using the NCBI database. We focused on tamoxifen resistance and its role in breast cancer. We then obtained a list of all genetic data and information about the genes and guiding pathways from the database. It is noteworthy that the best way to demonstrate this is through KEGG pathways and molecular docking pathways, which evaluate changes in DNA and histone methylation
- Results: The bioinformatics study provides strong evidence that EZH2 plays a role in establishing tamoxifen resistance in breast cancer through epigenetic changes. The ability of EZH2 to inhibit EZH2 fusions, such as L501-1669, in combination with tamoxifen, may provide a potential strategy to overcome drug resistance. . EZH2 may contribute to resistance through various mechanisms, including the activation of signalling pathways and the expression of tumour suppressor genes.
- Conclusion: This bioinformatic study highlights the pivotal role of EZH2 and epigenetic changes in tamoxifen resistance in breast cancer. EZH2 has been investigated through several mechanisms. However, challenges remain, such as differences in EZH2 mechanisms in different tissues, and the need for specific biomarkers
- Keywords: Breast cancer, epigenetic,EZH2
