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X Demographics
Mendeley readers
Attention Score in Context
| Title |
First in class dual MDM2/MDMX inhibitor ALRN-6924 enhances antitumor efficacy of chemotherapy in TP53 wild-type hormone receptor-positive breast cancer models
|
|---|---|
| Published in |
Breast Cancer Research, March 2021
|
| DOI | 10.1186/s13058-021-01406-x |
| Pubmed ID | |
| Authors |
Seyed Pairawan, Ming Zhao, Erkan Yuca, Allen Annis, Kurt Evans, David Sutton, Luis Carvajal, Jian-Guo Ren, Solimar Santiago, Vincent Guerlavais, Argun Akcakanat, Coya Tapia, Fei Yang, Priya Subash Chandra Bose, Xiaofeng Zheng, Ecaterina Ileana Dumbrava, Manuel Aivado, Funda Meric-Bernstam |
| Abstract |
MDM2/MDMX proteins are frequently elevated in hormone receptor-positive (ER+) breast cancer. We sought to determine the antitumor efficacy of the combination of ALRN-6924, a dual inhibitor of MDM2/MDMX, with chemotherapy in ER+ breast cancer models. Three hundred two cell lines representing multiple tumor types were screened to confirm the role of TP53 status in ALRN-6924 efficacy. ER+ breast cancer cell lines (MCF-7 and ZR-75-1) were used to investigate the antitumor efficacy of ALRN-6924 combination. In vitro cell proliferation, cell cycle, and apoptosis assays were performed. Xenograft tumor volumes were measured, and reverse-phase protein array (RPPA), immunohistochemistry (IHC), and TUNEL assay of tumor tissues were performed to evaluate the in vivo pharmacodynamic effects of ALRN-6924 with paclitaxel. ALRN-6924 was active in wild-type TP53 (WT-TP53) cancer cell lines, but not mutant TP53. On ER+ breast cancer cell lines, it was synergistic in vitro and had enhanced in vivo antitumor activity with both paclitaxel and eribulin. Flow cytometry revealed signs of mitotic crisis in all treatment groups; however, S phase was only decreased in MCF-7 single agent and combinatorial ALRN-6924 arms. RPPA and IHC demonstrated an increase in p21 expression in both combinatorial and single agent ALRN-6924 in vivo treatment groups. Apoptotic assays revealed a significantly enhanced in vivo apoptotic rate in ALRN-6924 combined with paclitaxel treatment arm compared to either single agent. The significant synergy observed with ALRN-6924 in combination with chemotherapeutic agents supports further evaluation in patients with hormone receptor-positive breast cancer. |
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 29 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 29 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 6 | 21% |
| Student > Master | 3 | 10% |
| Student > Doctoral Student | 2 | 7% |
| Student > Ph. D. Student | 2 | 7% |
| Student > Bachelor | 2 | 7% |
| Other | 2 | 7% |
| Unknown | 12 | 41% |
| Readers by discipline | Count | As % |
|---|---|---|
| Chemistry | 4 | 14% |
| Biochemistry, Genetics and Molecular Biology | 3 | 10% |
| Pharmacology, Toxicology and Pharmaceutical Science | 2 | 7% |
| Agricultural and Biological Sciences | 2 | 7% |
| Medicine and Dentistry | 2 | 7% |
| Other | 2 | 7% |
| Unknown | 14 | 48% |
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 05 March 2021.
All research outputs
#22,774,430
of 25,387,668 outputs
Outputs from Breast Cancer Research
#1,884
of 2,054 outputs
Outputs of similar age
#391,456
of 451,431 outputs
Outputs of similar age from Breast Cancer Research
#31
of 33 outputs
Altmetric has tracked 25,387,668 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 2,054 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 12.2. 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 451,431 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 33 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.