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X Demographics
Mendeley readers
Attention Score in Context
| Title |
A Synergistic Interaction between Chk1- and MK2 Inhibitors in KRAS-Mutant Cancer
|
|---|---|
| Published in |
Cell, July 2015
|
| DOI | 10.1016/j.cell.2015.05.053 |
| Pubmed ID | |
| Authors |
Felix Dietlein, Bastian Kalb, Mladen Jokic, Elisa M. Noll, Alexander Strong, Lars Tharun, Luka Ozretić, Helen Künstlinger, Kato Kambartel, Winfried J. Randerath, Christian Jüngst, Anna Schmitt, Alessandro Torgovnick, André Richters, Daniel Rauh, Florian Siedek, Thorsten Persigehl, Cornelia Mauch, Jirina Bartkova, Allan Bradley, Martin R. Sprick, Andreas Trumpp, Roland Rad, Dieter Saur, Jiri Bartek, Jürgen Wolf, Reinhard Büttner, Roman K. Thomas, H. Christian Reinhardt |
| Abstract |
KRAS is one of the most frequently mutated oncogenes in human cancer. Despite substantial efforts, no clinically applicable strategy has yet been developed to effectively treat KRAS-mutant tumors. Here, we perform a cell-line-based screen and identify strong synergistic interactions between cell-cycle checkpoint-abrogating Chk1- and MK2 inhibitors, specifically in KRAS- and BRAF-driven cells. Mechanistically, we show that KRAS-mutant cancer displays intrinsic genotoxic stress, leading to tonic Chk1- and MK2 activity. We demonstrate that simultaneous Chk1- and MK2 inhibition leads to mitotic catastrophe in KRAS-mutant cells. This actionable synergistic interaction is validated using xenograft models, as well as distinct Kras- or Braf-driven autochthonous murine cancer models. Lastly, we show that combined checkpoint inhibition induces apoptotic cell death in KRAS- or BRAF-mutant tumor cells directly isolated from patients. These results strongly recommend simultaneous Chk1- and MK2 inhibition as a therapeutic strategy for the treatment of KRAS- or BRAF-driven cancers. |
X Demographics
The data shown below were collected from the profiles of 22 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 9 | 41% |
| Germany | 2 | 9% |
| Ireland | 1 | 5% |
| Japan | 1 | 5% |
| Sweden | 1 | 5% |
| Israel | 1 | 5% |
| Unknown | 7 | 32% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 13 | 59% |
| Scientists | 7 | 32% |
| Practitioners (doctors, other healthcare professionals) | 2 | 9% |
Mendeley readers
The data shown below were compiled from readership statistics for 268 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Germany | 3 | 1% |
| United Kingdom | 2 | <1% |
| Japan | 2 | <1% |
| Spain | 1 | <1% |
| United States | 1 | <1% |
| Unknown | 259 | 97% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 64 | 24% |
| Student > Ph. D. Student | 52 | 19% |
| Student > Master | 22 | 8% |
| Student > Doctoral Student | 18 | 7% |
| Student > Bachelor | 16 | 6% |
| Other | 54 | 20% |
| Unknown | 42 | 16% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 75 | 28% |
| Biochemistry, Genetics and Molecular Biology | 65 | 24% |
| Medicine and Dentistry | 43 | 16% |
| Pharmacology, Toxicology and Pharmaceutical Science | 10 | 4% |
| Chemistry | 10 | 4% |
| Other | 15 | 6% |
| Unknown | 50 | 19% |
Attention Score in Context
This research output has an Altmetric Attention Score of 46. 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 21 February 2023.
All research outputs
#900,734
of 25,374,647 outputs
Outputs from Cell
#3,575
of 17,168 outputs
Outputs of similar age
#10,595
of 277,613 outputs
Outputs of similar age from Cell
#53
of 173 outputs
Altmetric has tracked 25,374,647 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 96th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 17,168 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 59.1. This one has done well, scoring higher than 79% of its peers.
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 277,613 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 96% of its contemporaries.
We're also able to compare this research output to 173 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 69% of its contemporaries.