Evidence map›Paper›PMID 20603437›Full record

Trial reportAnnals of oncology : official journal of the European Society for Medical Oncology2011

A let-7 microRNA-binding site polymorphism in 3'-untranslated region of KRAS gene predicts response in wild-type KRAS patients with metastatic colorectal cancer treated with cetuximab monotherapy.

W Zhang, T Winder, Y Ning, A Pohl, D Yang, M Kahn, G Lurje, M J LaBonte, P M Wilson, M A Gordon and 5 more

Open access · bronzeAbstract readClinical Trial, Phase II
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Annals of oncology : official journal of the European Society for Medical Oncology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed, 2 pooled it
8.3field-weighted citation impact, top 2% 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

64 citing papers in PubMed, 2 syntheses or guidelines pooled it, 134 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Trial
  5. Prognostic role of the LCS6 KRAS variant in locally advanced rectal cancer: results of the EXPERT-C trial.Annals of oncology : official journal of the European Society for Medical Oncology · 2015
    Trial
  6. Trial
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  9. Review
  10. Review
  11. Article
  12. Article
  13. Association of rs712 polymorphism in a let-7 microRNA-binding site ofIranian journal of basic medical sciences · 2019
    Article
  14. OncoTargets and therapy · 2019
    Article
  15. Article
  16. Article
  17. Review
  18. Review
  19. Article
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4 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 4 institutions in 2 countries.

W ZhangDivision of Medical Oncology.
T WinderDivision of Medical Oncology.
Y NingDivision of Medical Oncology.
A PohlDivision of Medical Oncology.
D YangDepartment of Preventive Medicine, University of Southern California/Norris Comprehensive Cancer Center, Keck School of Medicine, Los Angeles, CA, USA.
M KahnDivision of Medical Oncology.
G LurjeDepartment of Visceral- and Transplantation Surgery, University Hospital Zurich, Zurich, Switzerland.
M J LaBonteDepartment of Pathology, University of Southern California/Norris Comprehensive Cancer Center, Keck School of Medicine, Los Angeles, CA.
P M WilsonDepartment of Pathology, University of Southern California/Norris Comprehensive Cancer Center, Keck School of Medicine, Los Angeles, CA.
M A GordonDivision of Medical Oncology.
S Hu-LieskovanDivision of Medical Oncology.
D J MauroOncology, Merck & Co., Inc., NJ.
C LangerEarly Oncology, Bristol-Myers Squibb Pharmaceuticals Limited, New York.
E K RowinskyOncology, ImClone Systems, New York, NY, USA.
H-J LenzDivision of Medical Oncology; Department of Preventive Medicine, University of Southern California/Norris Comprehensive Cancer Center, Keck School of Medicine, Los Angeles, CA, USA. Electronic address: lenz@usc.edu.
University of Southern California · USBristol-Myers Squibb (United States) · USMerck & Co., Inc., Rahway, NJ, USA (United States) · USUniversity Hospital of Zurich · CH

Funding

USC/NORRIS COMPREHENSIVE CANCER CENTER (CORE) SUPPORTP30CA014089 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Fumito Ito · 1985 to 2026
$181.4M
NCI NIH HHS P30 CA014089
6 · The paper itself

Abstract

purposerecent studies have found that KRAS mutations predict resistance to monoclonal antibodies targeting the epidermal growth factor receptor in metastatic colorectal cancer (mCRC). A polymorphism in a let-7 microRNA complementary site (lcs6) in the KRAS 3' untranslated region (UTR) is associated with an increased cancer risk in non-small-cell lung cancer and reduced overall survival (OS) in oral cancers. We tested the hypothesis whether this polymorphism may be associated with clinical outcome in KRAS wild-type (KRASwt) mCRC patients treated with cetuximab monotherapy. PATIENTS AND

methodsthe presence of KRAS let-7 lcs6 polymorphism was evaluated in 130 mCRC patients who were enrolled in a phase II study of cetuximab monotherapy (IMCL-0144). Genomic DNA was extracted from dissected formalin-fixed paraffin-embedded tumor tissue, KRAS mutation status and polymorphism were assessed using direct sequencing and PCR restriction fragment length polymorphism technique.

resultsKRAS let-7 lcs6 polymorphism was found to be related to object response rate (ORR) in mCRC patients whose tumors had KRASwt. The 12 KRASwt patients harboring at least a variant G allele (TG or GG) had a 42% ORR compared with a 9% ORR in 55 KRASwt patients with let-7 lcs6 TT genotype (P = 0.02, Fisher's exact test). KRASwt patients with TG/GG genotypes had trend of longer median progression-free survival (3.9 versus 1.3 months) and OS (10.7 versus 6.4 months) compared to those with TT genotypes.

conclusionsthese results are the first to indicate that the KRAS 3'UTR polymorphism may predict for cetuximab responsiveness in KRASwt mCRC patients, which warrants validation in other clinical trials.

Indexed as

3' Untranslated RegionsGenes, rasAdultAgedAged, 80 and overAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic AgentsBinding SitesCetuximabColorectal NeoplasmsFemaleHumansMaleMicroRNAsMiddle Aged3' Untranslated RegionsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic AgentsCetuximabMicroRNAsmirnlet7 microRNA, human

Identifiers

PMID20603437
PMCPMC8890483
OpenAlexW2139920639

What OpenQuestion holds

Textmetadata
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.