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Most recent strategies targeting estrogen receptor alpha for the treatment of breast cancer

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Abstract

Breast cancer is the most prominent, frequently diagnosed and leading cause of death among women. Estrogen is an agonist of estrogen receptor alpha (ER-α), expressed in mammary glands and is responsible for initiating many signalling pathways that lead to differentiation and development of breast tissue. Any mutations in these signalling pathways result in irregular growth of mammary tissue, leading to the development of tumour or cancer. All these observations attract the attention of researchers to antagonize ER-α receptor either by developing selective estrogen receptor modulators or by selective estrogen receptor degraders. Therefore, this article provides a brief overview of various factors that are responsible for provoking breast cancer in women and design strategies recently used by the various research groups across the world for antagonizing or demodulating ER-α.

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Chapter © 2015

Chapter © 2017

Abbreviations

AF-1:

Activation factor-1

AF-2:

Activation factor-2

AKT:

Protein kinase B

AR:

Androgen receptor

Arg:

Arginine

Asp:

Aspartate

B.C.:

Before Christ

C.E.:

Common Era

CDH-1:

Cadherin-1

DBD:

DNA binding domain

DDT:

Dichlorodiphenyltrichloroethane

DDE:

Dichlorodiphenyldichloroethylene

DNA:

Deoxyribonucleic acid

EAC:

Ascites carcinoma

EGFR:

Epidermal growth factor receptor

ELISA:

Enzyme-linked immunosorbent assay

ER:

Estrogen receptor

ER-β:

Estrogen receptor beta

ER-α:

Estrogen receptor alpha

ERE:

Estrogen response elements

ERR-α:

Estrogen-related receptor-α

FDA:

Food and Drug Administration

Glu:

Glutamine

GSH:

Glutathione

HCB:

Hexachlorobenzene

HDACi:

Histone deacetylase inhibitors

HER-2:

Human epidermal growth factor receptor 2

HER-3:

Human epidermal growth factor receptor 3

His:

Histidine

IC50 :

Half maximal inhibitory concentration

IC-NST:

Invasive carcinoma of no special type

ICC:

Invasive cribriform carcinoma

ILC:

Invasive lobular carcinoma

Ile:

Isoleucine

kDa:

Kilo dalton

kB:

Kilo bases

LBD:

Ligand-binding domain

LDH:

Lactate dehydrogenase

Leu:

Leucine

LNCap:

Lymph node carcinoma of the prostate

LOX:

Lipoxygenase

MAPK:

Mitogen-activated protein kinase

Met:

Methionine

mM:

Milli-molar

nM:

Nano-molar

NSAIDs:

Non-steroidal anti-inflammatory drugs

NTD:

Nuclear terminal domain

OBHSA:

7-Oxabicyclo[2.2.1]heptene sulphonamide

PDB:

Protein Data Bank

Phe:

Phenylalanine

PI3 Kinase:

Phosphoinositide 3-kinases

PILC:

Pleomorphic invasive lobular carcinoma

SAR:

Structure activity relationship

SERDs:

Selective estrogen receptor degraders

SERMs:

Selective estrogen receptor modulators

TGF-β1:

Transforming growth factor beta 1

THIQ:

Tetrahydroisoquinoline

Thr:

Threonine

Trp:

Tryptophan

Tyr:

Tyrosine

µM:

Micro-molar

Val:

Valine

VEGFR:

Vascular endothelial growth factor

WHO:

World Health Organization

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Acknowledgements

Authors are grateful to the University Grants Commission for providing funds under, National Fellowship for Other Backward Classes (NFOBC) to AS, Rajiv Gandhi National Fellowship (RGNF) to HS, Council of Scientific and Industrial Research (CSIR: 02(0319)17/EMR-II) to JVS and funds under Component 4 of Rashtriya Uchchatar Shiksha Abhiyan (RUSA) scheme 2.0 to NK. The authors are also thankful to Guru Nanak Dev University, Amritsar for providing various basic facilities to complete the work.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab, 143005, India

    Nitish Kumar, Harmandeep Kaur Gulati, Aakriti Sharma, Shilpa Heer, Anupmjot Kaur Jassal, Lovenish Arora, Simranpreet Kaur, Atamjit Singh, Kavita Bhagat, Arshmeet Kaur, Harbinder Singh, Jatinder Vir Singh & Preet Mohinder Singh Bedi

  2. Drug and Pollution Testing Laboratory, Guru Nanak Dev University, Amritsar, Punjab, 143005, India

    Nitish Kumar & Preet Mohinder Singh Bedi

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  1. Nitish Kumar
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Kumar, N., Gulati, H.K., Sharma, A. et al. Most recent strategies targeting estrogen receptor alpha for the treatment of breast cancer. Mol Divers 25, 603–624 (2021). https://doi.org/10.1007/s11030-020-10133-y

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