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X Demographics
Mendeley readers
Attention Score in Context
| Title |
A Functional Cancer Genomics Screen Identifies a Druggable Synthetic Lethal Interaction between MSH3 and PRKDC
|
|---|---|
| Published in |
Cancer Discovery, May 2014
|
| DOI | 10.1158/2159-8290.cd-13-0907 |
| Pubmed ID | |
| Authors |
Felix Dietlein, Lisa Thelen, Mladen Jokic, Ron D. Jachimowicz, Laura Ivan, Gero Knittel, Uschi Leeser, Johanna van Oers, Winfried Edelmann, Lukas C. Heukamp, H. Christian Reinhardt |
| Abstract |
Here, we use a large-scale cell line-based approach to identify cancer cell-specific mutations that are associated with DNA-dependent protein kinase catalytic subunit (DNA-PKcs) dependence. For this purpose, we profiled the mutational landscape across 1,319 cancer-associated genes of 67 distinct cell lines and identified numerous genes involved in homologous recombination-mediated DNA repair, including BRCA1, BRCA2, ATM, PAXIP, and RAD50, as being associated with non-oncogene addiction to DNA-PKcs. Mutations in the mismatch repair gene MSH3, which have been reported to occur recurrently in numerous human cancer entities, emerged as the most significant predictors of DNA-PKcs addiction. Concordantly, DNA-PKcs inhibition robustly induced apoptosis in MSH3-mutant cell lines in vitro and displayed remarkable single-agent efficacy against MSH3-mutant tumors in vivo. Thus, we here identify a therapeutically actionable synthetic lethal interaction between MSH3 and the non-homologous end joining kinase DNA-PKcs. Our observations recommend DNA-PKcs inhibition as a therapeutic concept for the treatment of human cancers displaying homologous recombination defects. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 107 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 2 | 2% |
| China | 1 | <1% |
| Brazil | 1 | <1% |
| Unknown | 103 | 96% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 24 | 22% |
| Student > Ph. D. Student | 22 | 21% |
| Student > Bachelor | 11 | 10% |
| Professor > Associate Professor | 8 | 7% |
| Student > Doctoral Student | 6 | 6% |
| Other | 14 | 13% |
| Unknown | 22 | 21% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 34 | 32% |
| Biochemistry, Genetics and Molecular Biology | 25 | 23% |
| Medicine and Dentistry | 15 | 14% |
| Immunology and Microbiology | 2 | 2% |
| Economics, Econometrics and Finance | 1 | <1% |
| Other | 3 | 3% |
| Unknown | 27 | 25% |
Attention Score in Context
This research output has an Altmetric Attention Score of 4. 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 19 December 2019.
All research outputs
#7,061,613
of 23,577,654 outputs
Outputs from Cancer Discovery
#1,538
of 3,800 outputs
Outputs of similar age
#66,640
of 229,504 outputs
Outputs of similar age from Cancer Discovery
#18
of 54 outputs
Altmetric has tracked 23,577,654 research outputs across all sources so far. This one has received more attention than most of these and is in the 69th percentile.
So far Altmetric has tracked 3,800 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 20.7. This one has gotten more attention than average, scoring higher than 59% 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 229,504 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 70% of its contemporaries.
We're also able to compare this research output to 54 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 66% of its contemporaries.