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Journal of Endocrinology and Reproduction

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2022

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Chhetri, Dibyashree

Epigenetic Regulation of Tamoxifen-Resistant Breast Cancer: An Update

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Authors

Dibyashree Chhetri ¹, Dhanavathy Gnanasampanthapandian ¹, Kanagaraj Palaniyandi ¹

Affiliations
1 Cancer Science Laboratory, Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur - 603203, Chengalpattu, IN

Source

Journal of Endocrinology and Reproduction, Vol 26, No 4 (2022), Pagination: 221-237

Abstract

Breast cancer is the most common cause of death in women around the world. Epigenetic changes modulate transcriptional activity in several diseases, including cancer. Cancer epigenetics explains gene expression changes without DNA mutations. Aberrant DNA methylation, histone modifications, and mRNA expression promote tumоr growth and metastasis. In cancer cells, chemo-resistance occurs via Multidrug Resistance (MDR), apoptotic suppression, DNA damage response, epigenetic alterations, and competitive endogenous RNA. Owing to drug resistance, quiescence, and varied cancer cell production, Cancer Stem Cells (CSCs) are critical to tumоr formation, metastasis, and recurrence after therapy. In addition, MDR promotes drug efflux, enhanced secretion of growth factors, and DNA modifications in cancer patients, thereby causing fatalities in cancer patients. Heterogeneity and epigenetic plasticity cause drug resistance due to various factors. However, the molecular mechanism of epigenetic drug resistance is still unravelled completely. Overexpressed c-MYC leads to cancer and tamoxifen resistance. Despite the molecular underpinning of cancer development, drug resistance is continued in a myriad number of cases. Epigenetic changes affect CSCs viability and tumоr aggressiveness. These processes can be blocked by medicines. Tamoxifen is used widely for breast cancer treatment; however, latent treatments have emerged as a tamoxifen-resistant phenotype. Epigenetic modifications cause resistance by upregulating and altering the tumоr microenvironment and deregulating the immune response. The knowledge of epigenetic pathways in clinical treatment resistance may enhance the outcome of cancer patients. Multifactorial heterogeneous resistance is common in many targeted therapies. Many resistance mechanisms to targeted therapy may converge, including route reactivation. This review summarizes the epigenetic alterations, MDR, and development of tamoxifen resistance in breast cancer.

Keywords

Breast Cancer, Cancer Epigenetics, Cancer Stem Cells, Multidrug Resistance, Tamoxifen Resistance.

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