Evidence map›Paper›PMID 25183481›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2014

A let-7 microRNA-binding site polymorphism in KRAS predicts improved outcome in patients with metastatic colorectal cancer treated with salvage cetuximab/panitumumab monotherapy.

Zenia Saridaki, Joanne B Weidhaas, Heinz-Josef Lenz, Pierre Laurent-Puig, Bart Jacobs, Jef De Schutter, Wendy De Roock, David W Salzman, Wu Zhang, Dongyun Yang and 4 more

Registry-linked trialOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02253251 (Clinical Validation of the Role of microRNA Binding Site Mutations in Cancer Risk, Prevention and Treatment), which is not on this map. Cited by 34 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed, 3 pooled it
3.4field-weighted citation impact, top 6% 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.

NCT02253251 recruitingnot on this map

Clinical Validation of the Role of microRNA Binding Site Mutations in Cancer Risk, Prevention and Treatment

Typeobservational_patient_registrySponsorMiraKindRan2014 to 2035Enrolled15,000ConditionsCancerArmsKRAS-variant and microRNA binding site mutation testing
3 · Its place in the literature

Who cites it

34 citing papers in PubMed, 3 syntheses or guidelines pooled it, 59 citations in OpenAlex.

  1. mirSNPs as Potential Colorectal Cancer Biomarkers: A Systematic Review.International journal of molecular sciences · 2024
    Pooled it
  2. Pooled it
  3. Pooled it
  4. Trial
  5. Trial
  6. 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
  7. Article
  8. Review
  9. Review
  10. Article
  11. Review
  12. Article
  13. Article
  14. Oncology reviews · 2020
    Article
  15. Review
  16. Review
  17. Polymorphisms in microRNA let-7 binding sites of theAnnals of translational medicine · 2019
    Article
  18. Article
  19. The Dual Role of MicroRNAs in Colorectal Cancer Progression.International journal of molecular sciences · 2018
    Review
  20. Review
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

14 authors at 1 institution in 1 country.

Zenia Saridaki *Laboratory of Tumor Cell Biology School of Medicine, University of Crete, Heraklion, Greece.
Joanne B Weidhaas *Department of Therapeutic Radiology, Yale School of Medicine, New Haven, USA.
Heinz-Josef LenzDepartment of Medical Oncology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, USA.
Pierre Laurent-PuigUMR-S775 INSERM laboratory, Descartes University Medical School, Paris, France.
Bart JacobsLaboratory of Molecular Digestive Oncology, Department of Oncology , Katholieke Universiteit Leuven, Leuven, Belgium.
Jef De SchutterLaboratory of Molecular Digestive Oncology, Department of Oncology , Katholieke Universiteit Leuven, Leuven, Belgium.
Wendy De RoockOncology Unit, Ziekenhuis Oost-Limburg, Genk, Belgium.
David W SalzmanDepartment of Therapeutic Radiology, Yale School of Medicine, New Haven, USA.
Wu ZhangDepartment of Medical Oncology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, USA.
Dongyun YangDepartment of Preventive Medicine, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, USA.
Camilla PilatiFaculté de Médecine, Université Paris Descartes, Paris, France.
Olivier BouchéService d'Hépato Gastroentérologie et de Cancérologie Digestive, CHU Robert Debré, Reims, Champagne Ardenne, France.
Hubert PiessevauxCliniques Universitaires Saint-Luc, Université catholique de Louvain, Brussels, Belgium.
Sabine TejparLaboratory of Molecular Digestive Oncology, Department of Oncology , Katholieke Universiteit Leuven, Leuven, Belgium.
University of Crete · GR

Funding

MicroRNAs to Understand Cause and Outcome in Breast CancerR01CA157749 · NCI · YALE UNIVERSITY · PI SLACK, FRANK J., WEIDHAAS, JOANNE B · 2012 to 2016
$1.7M
Let-7 microRNAs in Lung Cancer: Altering Growth and RadioresistanceR01CA131301 · NCI · YALE UNIVERSITY · PI SLACK, FRANK J., WEIDHAAS, JOANNE B · 2009 to 2013
$1.7M
NCI NIH HHS CA131301-04NCI NIH HHS CA157749-01A1NCI NIH HHS R01 CA131301NCI NIH HHS R01 CA157749
6 · The paper itself

Abstract

purposeAn inherited mutation in KRAS (LCS6-variant or rs61764370) results in altered control of the KRAS oncogene. We studied this biomarker's correlation to anti-EGFR monoclonal antibody (mAb) therapy response in patients with metastatic colorectal cancer. EXPERIMENTAL

designLCS6-variant and KRAS/BRAF mutational status was determined in 512 patients with metastatic colorectal cancer treated with salvage anti-EGFR mAb therapy, and findings correlated with outcome. Reporters were tested in colon cancer cell lines to evaluate the differential response of the LCS6-variant allele to therapy exposure.

resultsIn this study, 21.2% (109 of 512) of patients with metastatic colorectal cancer had the LCS6-variant (TG/GG), which was found twice as frequently in the BRAF-mutated versus the wild-type (WT) group (P=0.03). LCS6-variant patients had significantly longer progression-free survival (PFS) with anti-EGFR mAb monotherapy treatment in the whole cohort (16.85 vs. 7.85 weeks; P=0.019) and in the double WT (KRAS and BRAF) patient population (18 vs. 10.4 weeks; P=0.039). Combination therapy (mAbs plus chemotherapy) led to improved PFS and overall survival (OS) for nonvariant patients, and brought their outcome to levels comparable with LCS6-variant patients receiving anti-EGFR mAb monotherapy. Combination therapy did not lead to improved PFS or OS for LCS6-variant patients. Cell line studies confirmed a unique response of the LCS6-variant allele to both anti-EGFR mAb monotherapy and chemotherapy.

conclusionsLCS6-variant patients with metastatic colorectal cancer have an excellent response to anti-EGFR mAb monotherapy, without any benefit from the addition of chemotherapy. These findings further confirm the importance of this mutation as a biomarker of anti-EGFR mAb response in patients with metastatic colorectal cancer, and warrant further prospective confirmation.

Indexed as

3' Untranslated RegionsAdultAgedAged, 80 and overAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedBinding SitesCetuximabColorectal NeoplasmsDisease-Free SurvivalFemaleGerm-Line MutationHumansMaleMicroRNAsMiddle Aged3' Untranslated RegionsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedCetuximabKRAS protein, humanMicroRNAsPanitumumabProto-Oncogene ProteinsProto-Oncogene Proteins p21(ras)ras Proteins

Identifiers

PMID25183481
PMCPMC4155520
OpenAlexW2088813500

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Registered trials

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.