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Proteolytic pan-RAS Cleavage Leads to Tumor Regression in Patient-derived Pancreatic Cancer Xenografts

Overview of attention for article published in Molecular Cancer Therapeutics, February 2022
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About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (85th percentile)
  • High Attention Score compared to outputs of the same age and source (91st percentile)

Mentioned by

twitter
23 tweeters

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3 Mendeley
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Title
Proteolytic pan-RAS Cleavage Leads to Tumor Regression in Patient-derived Pancreatic Cancer Xenografts
Published in
Molecular Cancer Therapeutics, February 2022
DOI 10.1158/1535-7163.mct-21-0550
Pubmed ID
Authors

Vania Vidimar, Minyoung Park, Caleb K. Stubbs, Nana K. Ingram, Wenan Qiang, Shanshan Zhang, Demirkan Gursel, Roman A. Melnyk, Karla J.F. Satchell

Abstract

The lack of effective RAS inhibition represents a major unmet medical need in the treatment of pancreatic ductal adenocarcinoma (PDAC). Here, we investigate the anticancer activity of RRSP-DTB, an engineered biologic that cleaves the Switch I of all RAS isoforms, in KRAS-mutant PDAC cell lines and patient-derived xenografts (PDXs). We first demonstrate that RRSP-DTB effectively engages RAS and impacts downstream ERK signaling in multiple KRAS-mutant PDAC cell lines inhibiting cell proliferation at picomolar concentrations. We next tested RRSP-DTB in immunodeficient mice bearing KRAS-mutant PDAC PDXs. Treatment with RRSP-DTB led to 95% tumor regression after 29 days. Residual tumors exhibited disrupted tissue architecture, increased fibrosis and fewer proliferating cells compared to controls. Intratumoral levels of phospho-ERK were also significantly lower, indicating in vivo target engagement. Importantly, tumors that started to regrow without RRSP-DTB shrank when treatment resumed, demonstrating resistance to RRSP-DTB had not developed. Tracking persistence of the toxin activity following intraperitoneal injection showed that RRSP-DTB is active in sera from immunocompetent mice for at least one hour, but absent after 16 hours, justifying use of daily dosing. Overall, we report that RRSP-DTB strongly regresses hard-to-treat KRAS-mutant PDX models of pancreatic cancer, warranting further development of this pan-RAS biologic for the management of RAS-addicted tumors.

Twitter Demographics

The data shown below were collected from the profiles of 23 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 3 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 3 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 1 33%
Student > Doctoral Student 1 33%
Unknown 1 33%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 1 33%
Medicine and Dentistry 1 33%
Unknown 1 33%

Attention Score in Context

This research output has an Altmetric Attention Score of 13. 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 26 May 2022.
All research outputs
#2,241,042
of 21,419,046 outputs
Outputs from Molecular Cancer Therapeutics
#281
of 3,702 outputs
Outputs of similar age
#47,611
of 336,864 outputs
Outputs of similar age from Molecular Cancer Therapeutics
#4
of 37 outputs
Altmetric has tracked 21,419,046 research outputs across all sources so far. Compared to these this one has done well and is in the 89th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 3,702 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 7.9. This one has done particularly well, scoring higher than 92% 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 336,864 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 85% of its contemporaries.
We're also able to compare this research output to 37 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 91% of its contemporaries.