Evidence map›Paper›PMID 27119512›Full record

ArticleOncotarget2016

Liquid biopsy monitoring uncovers acquired RAS-mediated resistance to cetuximab in a substantial proportion of patients with head and neck squamous cell carcinoma.

Friederike Braig, Minna Voigtlaender, Aneta Schieferdecker, Chia-Jung Busch, Simon Laban, Tobias Grob, Malte Kriegs, Rainald Knecht, Carsten Bokemeyer, Mascha Binder

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

Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed, 1 pooled it
6.1field-weighted citation impact, top 3% 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

37 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.

  1. Pooled it
  2. Tipifarnib in Head and Neck Squamous Cell Carcinoma WithJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2021
    Trial
  3. Review
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  8. New insights into RAS in head and neck cancer.Biochimica et biophysica acta. Reviews on cancer · 2023
    Review
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  10. Review
  11. Article
  12. Article
  13. Review
  14. Review
  15. Article
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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

10 authors at 3 institutions in 1 country.

Friederike BraigDepartment of Oncology and Hematology with Sections Bone Marrow Transplant and Pneumology, Hubertus Wald Tumorzentrum / University Cancer Center Hamburg, University Medical Center Hamburg, Hamburg, Germany.
Minna VoigtlaenderDepartment of Oncology and Hematology with Sections Bone Marrow Transplant and Pneumology, Hubertus Wald Tumorzentrum / University Cancer Center Hamburg, University Medical Center Hamburg, Hamburg, Germany.
Aneta SchieferdeckerDepartment of Oncology and Hematology with Sections Bone Marrow Transplant and Pneumology, Hubertus Wald Tumorzentrum / University Cancer Center Hamburg, University Medical Center Hamburg, Hamburg, Germany.
Chia-Jung BuschDepartment of Otorhinolaryngology, Head and Neck Cancer Center of The University Cancer Center Hamburg, University Medical Center Hamburg, Hamburg, Germany.
Simon LabanDepartment of Otorhinolaryngology, Head and Neck Cancer Center of The University Cancer Center Hamburg, University Medical Center Hamburg, Hamburg, Germany.
Tobias GrobDepartment of Pathology, University Medical Center Hamburg, Hamburg, Germany.
Malte KriegsLaboratory for Radiobiology and Experimental Radiooncology, Head and Neck Cancer Center of The University Cancer Center Hamburg, University Medical Center Hamburg, Hamburg, Germany.
Rainald KnechtDepartment of Otorhinolaryngology, Head and Neck Cancer Center of The University Cancer Center Hamburg, University Medical Center Hamburg, Hamburg, Germany.
Carsten BokemeyerDepartment of Oncology and Hematology with Sections Bone Marrow Transplant and Pneumology, Hubertus Wald Tumorzentrum / University Cancer Center Hamburg, University Medical Center Hamburg, Hamburg, Germany.
Mascha BinderDepartment of Oncology and Hematology with Sections Bone Marrow Transplant and Pneumology, Hubertus Wald Tumorzentrum / University Cancer Center Hamburg, University Medical Center Hamburg, Hamburg, Germany.
University Medical Center Hamburg-Eppendorf · DEUniversität Hamburg · DEUniversity Cancer Center Hamburg · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Resistance to epidermal growth factor receptor (EGFR)-targeted therapy is insufficiently understood in head and neck squamous cell carcinoma (HNSCC), entailing the lack of predictive biomarkers.Here, we studied resistance-mediating EGFR ectodomain and activating RAS mutations by next-generation sequencing (NGS) of cell lines and tumor tissue of cetuximab-naïve patients (46 cases, 12 cell lines), as well as liquid biopsies taken during and after cetuximab/platinum/5-fluorouracil treatment (20 cases). Tumors of cetuximab-naïve patients were unmutated, except for HRAS mutations in 4.3% of patients. Liquid biopsies revealed acquired KRAS, NRAS or HRAS mutations in more than one third of patients after cetuximab exposure. 46% of patients with on-treatment disease progression showed acquired RAS mutations, while no RAS mutations were found in the non-progressive subset of patients, indicating that acquisition of RAS mutant clones correlated significantly with clinical resistance (Chi square p=0.032). The emergence of mutations preceded clinical progression in half of the patients, with a maximum time from mutation detection to clinical progression of 16 weeks.RAS mutations account for acquired resistance to EGFR-targeting in a substantial proportion of HNSCC patients, even though these tumors are rarely mutated at baseline. Liquid biopsies may be used for mutational monitoring to guide treatment decisions.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsCarcinoma, Squamous CellCell Line, TumorCetuximabDrug Resistance, NeoplasmErbB ReceptorsFluorouracilGTP PhosphohydrolasesHead and Neck NeoplasmsHigh-Throughput Nucleotide SequencingHumansLiquid BiopsyMembrane ProteinsMutationPlatinumProto-Oncogene Proteins p21(ras)CetuximabEGFR protein, humanErbB ReceptorsFluorouracilGTP PhosphohydrolasesHRAS protein, humanKRAS protein, humanMembrane ProteinsNRAS protein, humanPlatinumProto-Oncogene Proteins p21(ras)ras Proteinscetuximabepidermal growth factor receptor (EGFR)head and neck squamous cell carcinoma (HNSCC)RASresistance

Identifiers

PMID27119512
PMCPMC5190002
OpenAlexW2339075220

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.