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Short-term early exposure to lapatinib confers lifelong protection from mammary tumor development in MMTV-erbB-2 transgenic mice

Overview of attention for article published in Journal of Experimental & Clinical Cancer Research, January 2017
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1 tweeter

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18 Mendeley
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Title
Short-term early exposure to lapatinib confers lifelong protection from mammary tumor development in MMTV-erbB-2 transgenic mice
Published in
Journal of Experimental & Clinical Cancer Research, January 2017
DOI 10.1186/s13046-016-0479-8
Pubmed ID
Authors

Zhikun Ma, Amanda B. Parris, Zhengzheng Xiao, Erin W. Howard, Stanley D. Kosanke, Xiaoshan Feng, Xiaohe Yang

Abstract

Although chemopreventative agents targeting the estrogen/estrogen receptor (ER) pathway have been effective for ER(+) breast cancers, prevention of hormone receptor-negative breast cancers, such as Her2/erbB-2(+) breast cancers, remains a significant issue. Previous studies have demonstrated that administration of EGFR/erbB-2-targeting lapatinib to MMTV-erbB-2 transgenic mice inhibited mammary tumor development. The prevention, however, was achieved by prolonged high dose exposure. The tolerance to high dose/long-term drug administration may hinder its potential in clinical settings. Therefore, we aimed to test a novel, short-term chemopreventative strategy using lapatinib during the premalignant risk window in MMTV-erbB-2 mice. We initially treated cultured cells with lapatinib to explore the anti-proliferative effects of lapatinib in vitro. We used a syngeneic tumor graft model to begin exploring the in vivo anti-tumorigenic effects of lapatinib in MMTV-erbB-2 mice. Then, we tested the efficacy of brief exposure to lapatinib (100 mg/kg/day for 8 weeks), beginning at 16 weeks of age, in the prevention of mammary tumor development in MMTV-erbB-2 mice. In the syngeneic tumor transplant model, we determined that lapatinib significantly inhibited tumor cell proliferation. Furthermore, we demonstrated that short-term lapatinib exposure resulted in life-long protective effects, as supported by increased tumor latency in lapatinib-treated mice compared to the control mice. We further established that delayed tumor development in the treated mice was preceded by decreased BrdU nuclear incorporation and inhibited mammary morphogenesis. Molecular analysis indicated that lapatinib inhibited phosphorylation and expression of EGFR, erbB-3, erbB-2, Akt1, and Erk1/2 in premalignant mammary tissues. Also, lapatinib drastically inhibited the phosphorylation and expression of ERα and the transcription of ER target genes in premalignant mammary tissues. We also determined that lapatinib suppressed the stemness of breast cancer cell lines, as evidenced by decreased tumorsphere formation and ALDH(+) cell populations. Taken together, these data demonstrate that brief treatment with EGFR/erbB-2-targeting agents before the onset of tumors may provide lifelong protection from mammary tumors, through the concurrent inhibition of erbB-2 and ER signaling pathways and consequential reprogramming. Our findings support further clinical testing to explore the benefit of shorter lapatinib exposure in the prevention of erbB-2-mediated carcinogenesis.

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 18 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 18 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 4 22%
Other 2 11%
Student > Ph. D. Student 2 11%
Student > Doctoral Student 1 6%
Student > Master 1 6%
Other 1 6%
Unknown 7 39%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 4 22%
Psychology 2 11%
Veterinary Science and Veterinary Medicine 1 6%
Medicine and Dentistry 1 6%
Neuroscience 1 6%
Other 0 0%
Unknown 9 50%

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 15 January 2017.
All research outputs
#9,990,100
of 12,480,907 outputs
Outputs from Journal of Experimental & Clinical Cancer Research
#413
of 768 outputs
Outputs of similar age
#279,488
of 397,204 outputs
Outputs of similar age from Journal of Experimental & Clinical Cancer Research
#47
of 106 outputs
Altmetric has tracked 12,480,907 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 768 research outputs from this source. They receive a mean Attention Score of 2.4. This one is in the 27th percentile – i.e., 27% 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 397,204 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 106 others from the same source and published within six weeks on either side of this one. This one is in the 30th percentile – i.e., 30% of its contemporaries scored the same or lower than it.