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Inhibition of PI3K/Akt/mTOR overcomes cisplatin resistance in the triple negative breast cancer cell line HCC38

Overview of attention for article published in BMC Cancer, November 2017
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Title
Inhibition of PI3K/Akt/mTOR overcomes cisplatin resistance in the triple negative breast cancer cell line HCC38
Published in
BMC Cancer, November 2017
DOI 10.1186/s12885-017-3695-5
Pubmed ID
Authors

Katharina Gohr, Alexandra Hamacher, Laura H. Engelke, Matthias U. Kassack

Abstract

Widely established targeted therapies directed at triple negative breast cancer (TNBC) are missing. Classical chemotherapy remains the systemic treatment option. Cisplatin has been tested in TNBC but bears the disadvantage of resistance development. The purpose of this study was to identify resistance mechanisms in cisplatin-resistant TNBC cell lines and select targeted therapies based on these findings. The TNBC cell lines HCC38 and MDA-MB231 were subjected to intermittent cisplatin treatment resulting in the 3.5-fold cisplatin-resistant subclone HCC38CisR and the 2.1-fold more resistant MDA-MB231CisR. Activation of pro-survival pathways was explored by immunostaining of phospho-receptor tyrosine kinases. Targeted therapies (NVP-AEW541, lapatinib and NVP-BEZ235) against activated pathways were investigated regarding cancer cell growth and cisplatin sensitivity. In HCC38CisR and MDA-MB231CisR, phosphorylation of epidermal growth factor receptor (EGFR) and insulin-like growth factor 1 receptor (IGF1R) was observed. In HCC38CisR, treatment with NVP-AEW541 increased potency of lapatinib almost seven-fold, but both compounds could not restore cisplatin sensitivity. However, the dual phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) inhibitor NVP-BEZ235 acted synergistically with cisplatin in HCC38CisR and fully restored cisplatin sensitivity. Similarly, NVP-BEZ235 increased cisplatin potency in MDA-MB231CisR. Furthermore, NVP-AEW541 in combination with lapatinib restored cisplatin sensitivity in MDA-MB231CisR. Simultaneous inhibition of EGFR and IGF1R in cisplatin-resistant TNBC cell lines was synergistic regarding inhibition of proliferation and induction of apoptosis. Co-treatment with NVP-BEZ235 or with a combination of NVP-AEW541 and lapatinib restored cisplatin sensitivity and may constitute a targeted treatment option for cisplatin-resistant TNBC.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 56 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 56 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 8 14%
Student > Master 8 14%
Researcher 8 14%
Student > Ph. D. Student 8 14%
Lecturer 3 5%
Other 6 11%
Unknown 15 27%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 18 32%
Pharmacology, Toxicology and Pharmaceutical Science 7 13%
Medicine and Dentistry 5 9%
Nursing and Health Professions 3 5%
Immunology and Microbiology 2 4%
Other 5 9%
Unknown 16 29%
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 13 November 2017.
All research outputs
#20,451,991
of 23,007,887 outputs
Outputs from BMC Cancer
#6,530
of 8,359 outputs
Outputs of similar age
#286,721
of 329,030 outputs
Outputs of similar age from BMC Cancer
#89
of 115 outputs
Altmetric has tracked 23,007,887 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 8,359 research outputs from this source. They receive a mean Attention Score of 4.3. This one is in the 1st percentile – i.e., 1% 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 329,030 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 115 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.