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Antitumor activity of the polo-like kinase inhibitor, TAK-960, against preclinical models of colorectal cancer

Overview of attention for article published in BMC Cancer, February 2018
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Title
Antitumor activity of the polo-like kinase inhibitor, TAK-960, against preclinical models of colorectal cancer
Published in
BMC Cancer, February 2018
DOI 10.1186/s12885-018-4036-z
Pubmed ID
Authors

Peter J. Klauck, Stacey M. Bagby, Anna Capasso, Erica L. Bradshaw-Pierce, Heather M. Selby, Anna Spreafico, John J. Tentler, Aik Choon Tan, Jihye Kim, John J. Arcaroli, Alicia Purkey, Wells A. Messersmith, Keisuke Kuida, S. Gail Eckhardt, Todd M. Pitts

Abstract

Polo-like kinase 1 (Plk1) is a serine/threonine kinase that is a key regulator of multiple stages of mitotic progression. Plk1 is upregulated in many tumor types including colorectal cancer (CRC) and portends a poor prognosis. TAK-960 is an ATP-competitive Plk1 inhibitor that has demonstrated efficacy across a broad range of cancer cell lines, including CRC. In this study, we investigated the activity of TAK-960 against a large collection of CRC models including 55 cell lines and 18 patient-derived xenografts. Fifty-five CRC cell lines and 18 PDX models were exposed to TAK-960 and evaluated for proliferation (IC50) and Tumor Growth Inhibition Index, respectively. Additionally, 2 KRAS wild type and 2 KRAS mutant PDX models were treated with TAK-960 as single agent or in combination with cetuximab or irinotecan. TAK-960 mechanism of action was elucidated through immunoblotting and cell cycle analysis. CRC cell lines demonstrated a variable anti-proliferative response to TAK-960 with IC50 values ranging from 0.001 to > 0.75 μmol/L. Anti-proliferative effects were sustained after removal of drug. Following TAK-960 treatment a highly variable accumulation of mitotic (indicating cell cycle arrest) and apoptotic markers was observed. Cell cycle analysis demonstrated that TAK-960 treatment induced G2/M arrest and polyploidy. Six out of the eighteen PDX models responded to single agent TAK-960 therapy (TGII< 20). The addition of TAK-960 to standard of care chemotherapy resulted in largely additive antitumor effects. TAK-960 is an active anti-proliferative agent against CRC cell lines and PDX models. Collectively, these data suggest that TAK-960 may be of therapeutic benefit alone or in combination with other agents, although future work should focus on the development of predictive biomarkers and hypothesis-driven rational combinations.

Twitter Demographics

The data shown below were collected from the profiles of 2 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 28 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 28 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 6 21%
Researcher 6 21%
Student > Ph. D. Student 4 14%
Student > Postgraduate 2 7%
Professor > Associate Professor 2 7%
Other 3 11%
Unknown 5 18%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 7 25%
Medicine and Dentistry 7 25%
Agricultural and Biological Sciences 3 11%
Psychology 1 4%
Immunology and Microbiology 1 4%
Other 2 7%
Unknown 7 25%

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 29 August 2021.
All research outputs
#16,378,905
of 20,370,630 outputs
Outputs from BMC Cancer
#4,611
of 7,295 outputs
Outputs of similar age
#292,246
of 392,871 outputs
Outputs of similar age from BMC Cancer
#2
of 4 outputs
Altmetric has tracked 20,370,630 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 7,295 research outputs from this source. They receive a mean Attention Score of 4.2. This one is in the 22nd percentile – i.e., 22% 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 392,871 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 14th percentile – i.e., 14% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 4 others from the same source and published within six weeks on either side of this one. This one has scored higher than 2 of them.