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X Demographics
Mendeley readers
Attention Score in Context
| Title |
Triple Targeting of HER Receptors Overcomes Heregulin-mediated Resistance to EGFR Blockade in Colorectal Cancer.
|
|---|---|
| Published in |
Molecular Cancer Therapeutics, February 2022
|
| DOI | 10.1158/1535-7163.mct-21-0818 |
| Pubmed ID | |
| Authors |
Alexander Rau, Nicole Janssen, Lennart Kühl, Thomas Sell, Svetlana Kalmykova, Thomas E Mürdter, Marc-H Dahlke, Christine Sers, Markus Morkel, Matthias Schwab, Roland E Kontermann, Monilola A Olayioye |
| Abstract |
Current treatment options for patients with advanced colorectal cancers (CRC) include anti-EGFR/HER1 therapy with the blocking antibody cetuximab. Although a subset of patients with KRAS wild-type disease initially respond to the treatment, resistance develops in almost all cases. Relapse has been associated with the production of the ligand heregulin (HRG) and/or compensatory signaling involving the receptor tyrosine kinases HER2 and HER3. Here we provide evidence that triple HER receptor blockade based on a newly developed bispecific EGFRxHER3-targeting antibody (scDb-Fc) together with the HER2 blocking antibody trastuzumab effectively inhibited HRG-induced HER receptor phosphorylation, downstream signaling, proliferation and stem cell expansion of DiFi and LIM1215 CRC cells. Comparative analyses revealed that the biological activity of scDb-Fc plus trastuzumab was sometimes even superior to that of the combination of the parental antibodies, with PI3K/Akt pathway inhibition correlating with improved therapeutic response and apoptosis induction as seen by single cell analysis. Importantly, growth suppression by triple HER targeting was recapitulated in primary KRAS wild-type patient-derived organoid (PDO) cultures exposed to HRG. Collectively, our results provide strong support for a pan-HER receptor blocking approach to combat anti-EGFR therapy resistance of KRAS wild-type CRC tumors mediated by the upregulation of HRG and/or HER2/HER3 signaling. |
X Demographics
The data shown below were collected from the profiles of 4 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Germany | 1 | 25% |
| Unknown | 3 | 75% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 3 | 75% |
| Science communicators (journalists, bloggers, editors) | 1 | 25% |
Mendeley readers
The data shown below were compiled from readership statistics for 17 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 17 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 3 | 18% |
| Lecturer | 2 | 12% |
| Student > Ph. D. Student | 2 | 12% |
| Student > Master | 1 | 6% |
| Professor | 1 | 6% |
| Other | 0 | 0% |
| Unknown | 8 | 47% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 6 | 35% |
| Nursing and Health Professions | 1 | 6% |
| Immunology and Microbiology | 1 | 6% |
| Unknown | 9 | 53% |
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 21 April 2023.
All research outputs
#13,908,131
of 23,578,918 outputs
Outputs from Molecular Cancer Therapeutics
#2,811
of 3,914 outputs
Outputs of similar age
#194,509
of 443,337 outputs
Outputs of similar age from Molecular Cancer Therapeutics
#36
of 64 outputs
Altmetric has tracked 23,578,918 research outputs across all sources so far. This one is in the 39th percentile – i.e., 39% of other outputs scored the same or lower than it.
So far Altmetric has tracked 3,914 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.6. 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 443,337 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 54% of its contemporaries.
We're also able to compare this research output to 64 others from the same source and published within six weeks on either side of this one. This one is in the 40th percentile – i.e., 40% of its contemporaries scored the same or lower than it.