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Oncotarget

Molecular mechanisms underlying resistance to androgen deprivation therapy in prostate cancer

Overview of attention for article published in Oncotarget, July 2016
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Title
Molecular mechanisms underlying resistance to androgen deprivation therapy in prostate cancer
Published in
Oncotarget, July 2016
DOI 10.18632/oncotarget.10901
Pubmed ID
Authors

Kristine M. Wadosky, Shahriar Koochekpour

Abstract

Prostate cancer (PCa) is the most widely diagnosed male cancer in the Western World and while low- and intermediate-risk PCa patients have a variety of treatment options, metastatic patients are limited to androgen deprivation therapy (ADT). This treatment paradigm has been in place for 75 years due to the unique role of androgens in promoting growth of prostatic epithelial cells via the transcription factor androgen receptor (AR) and downstream signaling pathways. Within 2 to 3 years of ADT, disease recurs-at which time, patients are considered to have castration-recurrent PCa (CR-PCa). A universal mechanism by which PCa becomes resistant to ADT has yet to be discovered. In this review article, we discuss underlying molecular mechanisms by which PCa evades ADT. Several major resistance pathways center on androgen signaling, including intratumoral and adrenal androgen production, AR-overexpression and amplification, expression of AR mutants, and constitutively-active AR splice variants. Other ADT resistance mechanisms, including activation of glucocorticoid receptor and impairment of DNA repair pathways are also discussed. New therapies have been approved for treatment of CR-PCa, but increase median survival by only 2-8 months. We discuss possible mechanisms of resistance to these new ADT agents. Finally, the practicality of the application of "precision oncology" to this continuing challenge of therapy resistance in metastatic or CR-PCa is examined. Empirical validation and clinical-based evidence are definitely needed to prove the superiority of "precision" treatment in providing a more targeted approach and curative therapies over the existing practices that are based on biological "cause-and-effect" relationship.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 143 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 143 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 27 19%
Student > Ph. D. Student 25 17%
Researcher 21 15%
Student > Bachelor 19 13%
Student > Postgraduate 6 4%
Other 19 13%
Unknown 26 18%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 41 29%
Medicine and Dentistry 31 22%
Agricultural and Biological Sciences 20 14%
Pharmacology, Toxicology and Pharmaceutical Science 7 5%
Unspecified 3 2%
Other 11 8%
Unknown 30 21%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. 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 07 February 2018.
All research outputs
#18,585,544
of 23,020,670 outputs
Outputs from Oncotarget
#8,470
of 14,344 outputs
Outputs of similar age
#283,196
of 366,485 outputs
Outputs of similar age from Oncotarget
#704
of 1,327 outputs
Altmetric has tracked 23,020,670 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 14,344 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.6. This one is in the 26th percentile – i.e., 26% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 366,485 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 12th percentile – i.e., 12% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 1,327 others from the same source and published within six weeks on either side of this one. This one is in the 31st percentile – i.e., 31% of its contemporaries scored the same or lower than it.