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Ohnmacht, A. ; Stahler, A.* ; Stintzing, S.* ; Modest, D.P.* ; Holch, J.W.* ; Westphalen, C.B.* ; Hölzel, L. ; Schübel, M.K. ; Galhoz, A. ; Farnoud, A. ; Ud-Dean, M. ; Vehling-Kaiser, U.* ; Decker, T.* ; Moehler, M.* ; Heinig, M. ; Heinemann, V.* ; Menden, M.P.

The Oncology Biomarker Discovery framework reveals cetuximab and bevacizumab response patterns in metastatic colorectal cancer.

Nat. Commun. 14:5391 (2023)
Publ. Version/Full Text DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Precision medicine has revolutionised cancer treatments; however, actionable biomarkers remain scarce. To address this, we develop the Oncology Biomarker Discovery (OncoBird) framework for analysing the molecular and biomarker landscape of randomised controlled clinical trials. OncoBird identifies biomarkers based on single genes or mutually exclusive genetic alterations in isolation or in the context of tumour subtypes, and finally, assesses predictive components by their treatment interactions. Here, we utilise the open-label, randomised phase III trial (FIRE-3, AIO KRK-0306) in metastatic colorectal carcinoma patients, who received either cetuximab or bevacizumab in combination with 5-fluorouracil, folinic acid and irinotecan (FOLFIRI). We systematically identify five biomarkers with predictive components, e.g., patients with tumours that carry chr20q amplifications or lack mutually exclusive ERK signalling mutations benefited from cetuximab compared to bevacizumab. In summary, OncoBird characterises the molecular landscape and outlines actionable biomarkers, which generalises to any molecularly characterised randomised controlled trial.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Folfiri Plus Cetuximab; Consensus Molecular Subtypes; Dna Topoisomerase-i; Subgroup Identification; Wild-type; Microsatellite Instability; Predictive Biomarkers; 1st-line Treatment; Open-label; Chemotherapy
Language english
Publication Year 2023
HGF-reported in Year 2023
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Journal Nature Communications
Quellenangaben Volume: 14, Issue: 1, Pages: , Article Number: 5391 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed
Institute(s) Institute of Computational Biology (ICB)
POF-Topic(s) 30205 - Bioengineering and Digital Health
Research field(s) Enabling and Novel Technologies
PSP Element(s) G-554700-001
G-503800-001
G-553500-001
Grants European Research Council (ERC)
Roche Pharma AG, Grenzach, Germany
Almac Ltd, Belfast, UK
Pfizer GmbH, Germany
Merck KGaA, Darmstadt, Germany
European Research Council (ERC) under the European Union
This project has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement No. 950293, M.P.M.). The clinical study received industrial funding from Merck KGaA, Darm
DOI 10.1038/s41467-023-41011-4
WOS ID 001169709500001
WOS ID 001072382600007
Scopus ID 85169688837
PubMed ID 37666855
Erfassungsdatum 2023-10-18
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