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Systematic drug screening reveals specific vulnerabilities and co-resistance patterns in endocrine-resistant breast cancer

Overview of attention for article published in BMC Cancer, July 2016
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1 tweeter

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45 Mendeley
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Title
Systematic drug screening reveals specific vulnerabilities and co-resistance patterns in endocrine-resistant breast cancer
Published in
BMC Cancer, July 2016
DOI 10.1186/s12885-016-2452-5
Pubmed ID
Authors

Sara Kangaspeska, Susanne Hultsch, Alok Jaiswal, Henrik Edgren, John-Patrick Mpindi, Samuli Eldfors, Oscar Brück, Tero Aittokallio, Olli Kallioniemi

Abstract

The estrogen receptor (ER) inhibitor tamoxifen reduces breast cancer mortality by 31 % and has served as the standard treatment for ER-positive breast cancers for decades. However, 50 % of advanced ER-positive cancers display de novo resistance to tamoxifen, and acquired resistance evolves in 40 % of patients who initially respond. Mechanisms underlying resistance development remain poorly understood and new therapeutic opportunities are urgently needed. Here, we report the generation and characterization of seven tamoxifen-resistant breast cancer cell lines from four parental strains. Using high throughput drug sensitivity and resistance testing (DSRT) with 279 approved and investigational oncology drugs, exome-sequencing and network analysis, we for the first time, systematically determine the drug response profiles specific to tamoxifen resistance. We discovered emerging vulnerabilities towards specific drugs, such as ERK1/2-, proteasome- and BCL-family inhibitors as the cells became tamoxifen-resistant. Co-resistance to other drugs such as the survivin inhibitor YM155 and the chemotherapeutic agent paclitaxel also occurred. This study indicates that multiple molecular mechanisms dictate endocrine resistance, resulting in unexpected vulnerabilities to initially ineffective drugs, as well as in emerging co-resistances. Thus, combatting drug-resistant tumors will require patient-tailored strategies in order to identify new drug vulnerabilities, and to understand the associated co-resistance patterns.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 45 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Finland 1 2%
Unknown 44 98%

Demographic breakdown

Readers by professional status Count As %
Student > Master 8 18%
Student > Ph. D. Student 6 13%
Student > Doctoral Student 5 11%
Researcher 5 11%
Student > Bachelor 4 9%
Other 5 11%
Unknown 12 27%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 9 20%
Agricultural and Biological Sciences 8 18%
Medicine and Dentistry 5 11%
Pharmacology, Toxicology and Pharmaceutical Science 4 9%
Chemistry 4 9%
Other 3 7%
Unknown 12 27%

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 05 July 2016.
All research outputs
#13,140,840
of 16,534,657 outputs
Outputs from BMC Cancer
#3,936
of 6,070 outputs
Outputs of similar age
#185,540
of 264,087 outputs
Outputs of similar age from BMC Cancer
#1
of 2 outputs
Altmetric has tracked 16,534,657 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 6,070 research outputs from this source. They receive a mean Attention Score of 4.1. This one is in the 20th percentile – i.e., 20% 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 264,087 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 17th percentile – i.e., 17% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 2 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them