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Drug-screening and genomic analyses of HER2-positive breast cancer cell lines reveal predictors for treatment response

Overview of attention for article published in Breast cancer targets and therapy, March 2017
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2 tweeters

Citations

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50 Mendeley
Title
Drug-screening and genomic analyses of HER2-positive breast cancer cell lines reveal predictors for treatment response
Published in
Breast cancer targets and therapy, March 2017
DOI 10.2147/bctt.s115600
Pubmed ID
Authors

Sandra Jernström, Vesa Hongisto, Suvi-Katri Leivonen, Eldri Undlien Due, Dagim Shiferaw Tadele, Henrik Edgren, Olli Kallioniemi, Merja Perälä, Gunhild Mari Mælandsmo, Kristine Kleivi Sahlberg

Abstract

Approximately 15%-20% of all diagnosed breast cancers are characterized by amplified and overexpressed HER2 (= ErbB2). These breast cancers are aggressive and have a poor prognosis. Although improvements in treatment have been achieved after the introduction of trastuzumab and lapatinib, many patients do not benefit from these drugs. Therefore, in-depth understanding of the mechanisms behind the treatment responses is essential to find alternative therapeutic strategies. Thirteen HER2 positive breast cancer cell lines were screened with 22 commercially available compounds, mainly targeting proteins in the ErbB2-signaling pathway, and molecular mechanisms related to treatment sensitivity were sought. Cell viability was measured, and treatment responses between the cell lines were compared. To search for response predictors and genomic and transcriptomic profiling, PIK3CA mutations and PTEN status were explored and molecular features associated with drug sensitivity sought. The cell lines were divided into three groups according to the growth-retarding effect induced by trastuzumab and lapatinib. Interestingly, two cell lines insensitive to trastuzumab (KPL4 and SUM190PT) showed sensitivity to an Akt1/2 kinase inhibitor. These cell lines had mutation in PIK3CA and loss of PTEN, suggesting an activated and druggable Akt-signaling pathway. Expression levels of five genes (CDC42, MAPK8, PLCG1, PTK6, and PAK6) were suggested as predictors for the Akt1/2 kinase-inhibitor response. Targeting the Akt-signaling pathway shows promise in cell lines that do not respond to trastuzumab. In addition, our results indicate that several molecular features determine the growth-retarding effects induced by the drugs, suggesting that parameters other than HER2 amplification/expression should be included as markers for therapy decisions.

Twitter Demographics

The data shown below were collected from the profiles of 2 tweeters 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 50 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
China 1 2%
Unknown 49 98%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 14 28%
Student > Bachelor 8 16%
Researcher 7 14%
Student > Master 6 12%
Professor > Associate Professor 2 4%
Other 4 8%
Unknown 9 18%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 14 28%
Agricultural and Biological Sciences 10 20%
Engineering 3 6%
Medicine and Dentistry 3 6%
Pharmacology, Toxicology and Pharmaceutical Science 3 6%
Other 6 12%
Unknown 11 22%

Attention Score in Context

This research output has an Altmetric Attention Score of 2. 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 31 March 2017.
All research outputs
#4,776,873
of 9,272,034 outputs
Outputs from Breast cancer targets and therapy
#79
of 138 outputs
Outputs of similar age
#137,285
of 260,290 outputs
Outputs of similar age from Breast cancer targets and therapy
#12
of 17 outputs
Altmetric has tracked 9,272,034 research outputs across all sources so far. This one is in the 45th percentile – i.e., 45% of other outputs scored the same or lower than it.
So far Altmetric has tracked 138 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 7.8. This one is in the 39th percentile – i.e., 39% 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 260,290 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 43rd percentile – i.e., 43% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 17 others from the same source and published within six weeks on either side of this one. This one is in the 29th percentile – i.e., 29% of its contemporaries scored the same or lower than it.