Estrogen alpha receptor antagonists for the treatment of breast cancer: a review

Sharma, Deepika; Kumar, Sanjiv

doi:10.1186/s13065-018-0472-8

Cited by 83 publications

(61 citation statements)

References 47 publications

(54 reference statements)

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“…Initially, these renal tumors are transplantable only to those hamsters that are treated with estrogen, connoting that the tumors still depend on an excessive amount of estrogen, but autonomy can eventually be achieved by manipulation of the estrogen in the recipient animals [119,159,160]. The hormone dependency seen in all of these studies is the rationale behind the anti-hormone treatments of hormone-dependent cancers [161][162][163].…”

Section: Hormone-induced Tumors In Animals Are Inducer-dependent Untimentioning

confidence: 99%

Evidence for immortality and autonomy in animal cancer models is often not provided, which causes confusion on key issues of cancer biology

Dou¹,

Tong²,

Huang³

et al. 2020

J. Cancer

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Modern research into carcinogenesis has undergone three phases. Surgeons and pathologists started the first phase roughly 250 years ago, establishing morphological traits of tumors for pathologic diagnosis, and setting immortality and autonomy as indispensable criteria for neoplasms. A century ago, medical doctors, biologists and chemists started to enhance "experimental cancer research" by establishing many animal models of chemical-induced carcinogenesis for studies of cellular mechanisms. In this second phase, the two-hit theory and stepwise carcinogenesis of "initiation-promotion" or "initiation-promotion-progression" were established, with an illustrious finding that outgrowths induced in animals depend on the inducers, and thus are not authentically neoplastic, until late stages. The last 40 years are the third incarnation, molecular biologists have gradually dominated the carcinogenesis research fraternity and have established numerous genetically-modified animal models of carcinogenesis. However, evidence has not been provided for immortality and autonomy of the lesions from most of these models. Probably, many lesions had already been collected from animals for analyses of molecular mechanisms of "cancer" before the lesions became autonomous. We herein review the monumental work of many predecessors to reinforce that evidence for immortality and autonomy is essential for confirming a neoplastic nature. We extrapolate that immortality and autonomy are established early during sporadic human carcinogenesis, unlike the late establishment in most animal models. It is imperative to resume many forerunners' work by determining the genetic bases for initiation, promotion and progression, the genetic bases for immortality and autonomy, and which animal models are, in fact, good for identifying such genetic bases.

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Section: Hormone-induced Tumors In Animals Are Inducer-dependent Untimentioning

confidence: 99%

Evidence for immortality and autonomy in animal cancer models is often not provided, which causes confusion on key issues of cancer biology

Dou¹,

Tong²,

Huang³

et al. 2020

J. Cancer

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“…The first SERMs, such as tamoxifen (TMX) and toremifene, are used in the treatment of breast cancer. TMX can act as an ERα antagonist and agonist [224]. TMX crosses the BBB [225] and exerts an E2-like neuroprotective effect in the brain without the peripheral side effects observed in estrogen therapy [226].…”

Section: Potential Therapeutic Interventions With Estrogenic Compoundmentioning

confidence: 99%

The Role of Estradiol in Traumatic Brain Injury: Mechanism and Treatment Potential

Kövesdi

Szabó-Meleg

Ábrahám

2020

IJMS

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Patients surviving traumatic brain injury (TBI) face numerous neurological and neuropsychological problems significantly affecting their quality of life. Extensive studies over the past decades have investigated pharmacological treatment options in different animal models, targeting various pathological consequences of TBI. Sex and gender are known to influence the outcome of TBI in animal models and in patients, respectively. Apart from its well-known effects on reproduction, 17β-estradiol (E2) has a neuroprotective role in brain injury. Hence, in this review, we focus on the effect of E2 in TBI in humans and animals. First, we discuss the clinical classification and pathomechanism of TBI, the research in animal models, and the neuroprotective role of E2. Based on the results of animal studies and clinical trials, we discuss possible E2 targets from early to late events in the pathomechanism of TBI, including neuroinflammation and possible disturbances of the endocrine system. Finally, the potential relevance of selective estrogenic compounds in the treatment of TBI will be discussed.

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“…Tamoxifen was the only approved anti-estrogen for BCa treatment until 1997, when toremifene also passed FDA approval [ 162 , 163 ]. It demonstrated similar tolerability and safety as tamoxifen and its long-term administration also elevated the risk of endometrial cancer development [ 164 ]. On the other hand, while toremifene was found to be three times less potent than tamoxifen, it was characterized as less carcinogenic compared to tamoxifen.…”

Section: Small Molecule Inhibitorsmentioning

confidence: 99%

Computer-Aided Ligand Discovery for Estrogen Receptor Alpha

Bafna

Ban

Rennie

et al. 2020

IJMS

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Breast cancer (BCa) is one of the most predominantly diagnosed cancers in women. Notably, 70% of BCa diagnoses are Estrogen Receptor α positive (ERα+) making it a critical therapeutic target. With that, the two subtypes of ER, ERα and ERβ, have contrasting effects on BCa cells. While ERα promotes cancerous activities, ERβ isoform exhibits inhibitory effects on the same. ER-directed small molecule drug discovery for BCa has provided the FDA approved drugs tamoxifen, toremifene, raloxifene and fulvestrant that all bind to the estrogen binding site of the receptor. These ER-directed inhibitors are non-selective in nature and may eventually induce resistance in BCa cells as well as increase the risk of endometrial cancer development. Thus, there is an urgent need to develop novel drugs with alternative ERα targeting mechanisms that can overcome the limitations of conventional anti-ERα therapies. Several functional sites on ERα, such as Activation Function-2 (AF2), DNA binding domain (DBD), and F-domain, have been recently considered as potential targets in the context of drug research and discovery. In this review, we summarize methods of computer-aided drug design (CADD) that have been employed to analyze and explore potential targetable sites on ERα, discuss recent advancement of ERα inhibitor development, and highlight the potential opportunities and challenges of future ERα-directed drug discovery.

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Estrogen alpha receptor antagonists for the treatment of breast cancer: a review

Cited by 83 publications

References 47 publications

Evidence for immortality and autonomy in animal cancer models is often not provided, which causes confusion on key issues of cancer biology

Evidence for immortality and autonomy in animal cancer models is often not provided, which causes confusion on key issues of cancer biology

The Role of Estradiol in Traumatic Brain Injury: Mechanism and Treatment Potential

Computer-Aided Ligand Discovery for Estrogen Receptor Alpha

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