| Title |
The pitfall of the transient, inconsistent anticancer capacity of antiestrogens and the mechanism of apparent antiestrogen resistance
|
|---|---|
| Published in |
Drug Design, Development and Therapy, August 2015
|
| DOI | 10.2147/dddt.s89536 |
| Pubmed ID | |
| Authors |
Zsuzsanna Suba |
| Abstract |
Although antiestrogens have been available for breast cancer therapy since the early 1970s, neither their inconsistent anticancer capacity nor the developing antiestrogen resistance of tumors can be fully understood. Although clinical and experimental investigations revealed many tiny details concerning the link between estrogen signaling and tumor development, they yielded fairly controversial findings. Estrogen receptor (ER) overexpression in tumor cells induced by estrogen treatment was erroneously regarded as a promoter of DNA damage, genomic instability, and tumor growth. Similarly, compensatory ER overexpression caused by antiestrogen treatment or estrogen withdrawal was mistakenly evaluated as a key for rapid tumor growth attributed to acquired antiestrogen resistance. Nevertheless, ER upregulation induced by estrogen treatment is a physiologic process even in tumor cells, whereas in the case of antiestrogen administration, it is a contraregulatory action to defend the endangered estrogen signaling. Upregulation of estrogen signaling displays a unique dichotomy, ensuring the survival and safe proliferative activity of healthy cells, while inducing apoptotic death of malignant tumor cells. Analysis of the fairly controversial results justifies that whatever type of available endocrine therapies may be used, including estrogen, antiestrogen treatment, or oophorectomy, an extreme upregulation of ER signaling seems to be the crucial mechanism of successful prevention and treatment for breast cancer. The inconsistent therapeutic effects of antiestrogen administration may be explained by the different genetic capacities of patients for the compensatory upregulation of ER and aromatase enzyme expressions. The weaker the defensive counteraction against the inhibition of estrogen signaling, the poorer is the prognosis of the disease. De novo or acquired antiestrogen resistance of tumors may be associated with the missing capacity of patients for the extreme upregulation of estrogen signaling or with the exhaustion of defensive counteractions in cases that previously showed good reactivity. High-dose estrogen treatment is capable of restoring ER signaling and anticancer capacity even after heavy exposure to antiestrogen therapy. |
X Demographics
The data shown below were collected from the profiles of 5 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 1 | 20% |
| Hungary | 1 | 20% |
| Unknown | 3 | 60% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 5 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 12 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 12 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 3 | 25% |
| Student > Doctoral Student | 2 | 17% |
| Researcher | 2 | 17% |
| Student > Bachelor | 1 | 8% |
| Other | 1 | 8% |
| Other | 1 | 8% |
| Unknown | 2 | 17% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 4 | 33% |
| Biochemistry, Genetics and Molecular Biology | 2 | 17% |
| Nursing and Health Professions | 2 | 17% |
| Agricultural and Biological Sciences | 1 | 8% |
| Chemical Engineering | 1 | 8% |
| Other | 0 | 0% |
| Unknown | 2 | 17% |
Attention Score in Context
This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 05 February 2024.
All research outputs
#15,092,197
of 25,374,917 outputs
Outputs from Drug Design, Development and Therapy
#813
of 2,268 outputs
Outputs of similar age
#133,134
of 276,431 outputs
Outputs of similar age from Drug Design, Development and Therapy
#49
of 151 outputs
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We're also able to compare this research output to 151 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 67% of its contemporaries.