Evidence map›Paper›PMID 26136684›Full record

ArticleFrontiers in pharmacology2015

Combined inhibition of MEK and Aurora A kinase in KRAS/PIK3CA double-mutant colorectal cancer models.

S Lindsey Davis, Kelli M Robertson, Todd M Pitts, John J Tentler, Erica L Bradshaw-Pierce, Peter J Klauck, Stacey M Bagby, Stephanie L Hyatt, Heather M Selby, Anna Spreafico and 5 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Frontiers in pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
2.0field-weighted citation impact, top 15% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 26 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Review
  14. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 4 institutions in 1 country.

S Lindsey DavisDivision of Medical Oncology, Department of Internal Medicine, University of Colorado Anschutz Medical Campus Aurora, CO, USA ; University of Colorado Cancer Center, University of Colorado Anschutz Medical Campus Aurora, CO, USA.
Kelli M RobertsonDivision of Medical Oncology, Department of Internal Medicine, University of Colorado Anschutz Medical Campus Aurora, CO, USA.
Todd M PittsDivision of Medical Oncology, Department of Internal Medicine, University of Colorado Anschutz Medical Campus Aurora, CO, USA ; University of Colorado Cancer Center, University of Colorado Anschutz Medical Campus Aurora, CO, USA.
John J TentlerDivision of Medical Oncology, Department of Internal Medicine, University of Colorado Anschutz Medical Campus Aurora, CO, USA ; University of Colorado Cancer Center, University of Colorado Anschutz Medical Campus Aurora, CO, USA.
Erica L Bradshaw-PierceUniversity of Colorado Cancer Center, University of Colorado Anschutz Medical Campus Aurora, CO, USA ; Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus Aurora, CO, USA ; Department of Drug Metabolism and Pharmacokinetics, Takeda California, Inc. San Diego, CA, USA.
Peter J KlauckDivision of Medical Oncology, Department of Internal Medicine, University of Colorado Anschutz Medical Campus Aurora, CO, USA.
Stacey M BagbyDivision of Medical Oncology, Department of Internal Medicine, University of Colorado Anschutz Medical Campus Aurora, CO, USA.
Stephanie L HyattDivision of Medical Oncology, Department of Internal Medicine, University of Colorado Anschutz Medical Campus Aurora, CO, USA.
Heather M SelbyDivision of Medical Oncology, Department of Internal Medicine, University of Colorado Anschutz Medical Campus Aurora, CO, USA.
Anna SpreaficoDivision of Medical Oncology, Department of Internal Medicine, University of Colorado Anschutz Medical Campus Aurora, CO, USA.
Jeffrey A EcsedyDepartment of Translational Medicine, Millenium Pharmaceuticals, Inc., A wholly owned Subsidiary of a Takeda Pharmaceutical Company Limited Cambridge, MA, USA.
John J ArcaroliDivision of Medical Oncology, Department of Internal Medicine, University of Colorado Anschutz Medical Campus Aurora, CO, USA ; University of Colorado Cancer Center, University of Colorado Anschutz Medical Campus Aurora, CO, USA.
Wells A MessersmithDivision of Medical Oncology, Department of Internal Medicine, University of Colorado Anschutz Medical Campus Aurora, CO, USA ; University of Colorado Cancer Center, University of Colorado Anschutz Medical Campus Aurora, CO, USA.
Aik Choon TanUniversity of Colorado Cancer Center, University of Colorado Anschutz Medical Campus Aurora, CO, USA.
S Gail EckhardtDivision of Medical Oncology, Department of Internal Medicine, University of Colorado Anschutz Medical Campus Aurora, CO, USA ; University of Colorado Cancer Center, University of Colorado Anschutz Medical Campus Aurora, CO, USA.
University of Colorado Anschutz Medical Campus · USUniversity of Colorado Cancer Center · USUniversity of Colorado Denver · USTakeda (United States) · US

Funding

University of Colorado Cancer Center Support Grant - Lung Cancer Patient-Derived Xenografts with Autologous Human Immune SystemsP30CA046934 · NCI · UNIVERSITY OF COLORADO DENVER · PI James V Degregori · 1988 to 2026
$117.0M
NCI NIH HHS P30 CA046934
6 · The paper itself

Abstract

Aurora A kinase and MEK inhibitors induce different, and potentially complementary, effects on the cell cycle of malignant cells, suggesting a rational basis for utilizing these agents in combination. In this work, the combination of an Aurora A kinase and MEK inhibitor was evaluated in pre-clinical colorectal cancer models, with a focus on identifying a subpopulation in which it might be most effective. Increased synergistic activity of the drug combination was identified in colorectal cancer cell lines with concomitant KRAS and PIK3CA mutations. Anti-proliferative effects were observed upon treatment of these double-mutant cell lines with the drug combination, and tumor growth inhibition was observed in double-mutant human tumor xenografts, though effects were variable within this subset. Additional evaluation suggests that degree of G2/M delay and p53 mutation status affect apoptotic activity induced by combination therapy with an Aurora A kinase and MEK inhibitor in KRAS and PIK3CA mutant colorectal cancer. Overall, in vitro and in vivo testing was unable to identify a subset of colorectal cancer that was consistently responsive to the combination of a MEK and Aurora A kinase inhibitor.

Indexed as

alisertibAurora A kinasecolorectal cancerhuman tumor xenograftsKRAS mutationMEKPIK3CAtrametinib

Identifiers

PMID26136684
PMCPMC4468631
OpenAlexW1599556954

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.