Evidence map›Paper›PMID 33901792›Full record

ArticleEuropean journal of cancer (Oxford, England : 1990)2021

Germ line polymorphisms of genes involved in pluripotency transcription factors predict efficacy of cetuximab in metastatic colorectal cancer.

Hiroyuki Arai, Joshua Millstein, Fotios Loupakis, Sebastian Stintzing, Jingyuan Wang, Francesca Battaglin, Natsuko Kawanishi, Priya Jayachandran, Shivani Soni, Wu Zhang and 5 more

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

Article in European journal of cancer (Oxford, England : 1990), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.2field-weighted citation impact, top 48% 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

1 citing paper in PubMed, 2 citations in OpenAlex.

  1. 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

15 authors at 5 institutions in 3 countries.

Hiroyuki AraiDivision of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, USA.
Joshua MillsteinDepartment of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, USA.
Fotios LoupakisClinical and Experimental Oncology Department, Medical Oncology Unit 1, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy.
Sebastian StintzingMedical Department, Division of Hematology, Oncology, and Tumour Immunology (CCM), Charité - Universitaetsmedizin, Berlin, Germany.
Jingyuan WangDivision of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, USA.
Francesca BattaglinDivision of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, USA.
Natsuko KawanishiDivision of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, USA.
Priya JayachandranDivision of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, USA.
Shivani SoniDivision of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, USA.
Wu ZhangDivision of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, USA.
Shannon M MumenthalerLawrence J. Ellison Institute for Transformative Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, USA.
Chiara CremoliniDepartment of Translational Medicine, Division of Medical Oncology, University of Pisa, Pisa, Italy.
Volker HeinemannDepartment of Medicine III, University Hospital, LMU Munich, Munich, Germany.
Alfredo FalconeDepartment of Translational Medicine, Division of Medical Oncology, University of Pisa, Pisa, Italy.
Heinz-Josef LenzDivision of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, USA. Electronic address: lenz@usc.edu.
University of Southern California · USUniversity of Pisa · ITCharité - Universitätsmedizin Berlin · DEIstituto Oncologico Veneto · ITLMU Klinikum · DE

Funding

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

Abstract

backgroundCancer stem cells (CSCs) are primarily maintained by a network of pluripotency transcription factors (PTFs). Given a close relationship of CSC regulation with epidermal growth factor receptor and vascular endothelial growth factor signalling, we investigated whether single-nucleotide polymorphisms (SNPs) in PTF genes are related to the efficacy of cetuximab and/or bevacizumab in patients with metastatic colorectal cancer (mCRC). PATIENTS AND

methodsGenomic and clinical data from three independent clinical trial cohorts were tested: cetuximab cohort (FOLFIRI/cetuximab arm in FIRE-3, n = 129), bevacizumab cohort 1 (FOLFIRI/bevacizumab arm in FIRE-3, n = 107) and bevacizumab cohort 2 (FOLFIRI/bevacizumab arm in TRIBE, n = 215). Genomic DNA extracted from blood samples was genotyped, and ten SNPs were tested for association with clinical outcomes.

resultsIn the cetuximab cohort, four SNPs were significantly associated with progression-free survival in univariate analysis: NANOG rs11055767 (any A allele vs C/C, hazard ratio [HR] = 0.62, 95% confidence interval [CI] = 0.42-0.94, p = 0.02), NANOG rs10744044 (any A allele vs G/G, HR = 0.59, 95% CI = 0.39-0.90, p = 0.01), NANOGP8 rs2168958 (any C allele vs A/A, HR = 2.12, 95% CI = 1.36-3.29, p < 0.001) and NANOGP8 rs2279066 (any C allele vs T/T, HR = 1.80, 95% CI = 1.06-1.68, p = 0.03). Multivariate analysis confirmed the significant associations for NANOGP8 rs2168958 and NANOGP8 rs2279066. In either bevacizumab cohort, no significant associations were observed in univariate analysis.

conclusionsGerm line polymorphisms in the PTF genes could be predictive markers for cetuximab in mCRC.

Indexed as

Polymorphism, Single NucleotideAntineoplastic Agents, ImmunologicalAntineoplastic Combined Chemotherapy ProtocolsBevacizumabBiomarkers, TumorCetuximabClinical Trials, Phase III as TopicColorectal NeoplasmsGenetic Predisposition to DiseaseHumansNanog Homeobox ProteinNeoplasm MetastasisNeoplastic Stem CellsPhenotypeProgression-Free SurvivalRandomized Controlled Trials as TopicAntineoplastic Agents, ImmunologicalBevacizumabBiomarkers, TumorCetuximabNanog Homeobox ProteinNANOG protein, humanBiomarkerCancer stem cellCetuximabColorectal cancerNANOG

Identifiers

PMID33901792
PMCPMC12047410
OpenAlexW3157337076

What OpenQuestion holds

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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.