Evidence map›Paper›PMID 41882736›Full record

ArticleJournal of experimental & clinical cancer research : CR2026

BRAF

Anna Kotarac, Hiroki Osumi, Alexander Malt, Keziban Merve Alp, Armin Jarosch, Johannes Werner, Manuela Benary, Christopher C M Neumann, Ryoji Yao, Philipp Mertins and 7 more

Abstract read
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

17 authors.

Anna KotaracCharité Comprehensive Cancer Center, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Hiroki OsumiDepartment of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
Alexander Malt *Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Center of Digital Health, Berlin, Germany.
Keziban Merve Alp *Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Center of Digital Health, Berlin, Germany.
Armin JaroschDepartment of Pathology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Johannes WernerCharité Comprehensive Cancer Center, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Manuela BenaryCharité Comprehensive Cancer Center, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Christopher C M NeumannDepartment of Hematology, Oncology, and Cancer Immunology, (CCM), Charité - Universitätsmedizin Berlin, Berlin, Germany.
Ryoji YaoDepartment of Cell Biology, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan.
Philipp MertinsBerlin Institute of Health at Charité - Universitätsmedizin Berlin, Center of Digital Health, Berlin, Germany.
Roland EilsBerlin Institute of Health at Charité - Universitätsmedizin Berlin, Center of Digital Health, Berlin, Germany.
Dieter BeuleBIH-Core Unit Bioinformatics, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Christine SersGerman Cancer Consortium (DKTK), Partner Site Berlin, Germany.
Ulrich KeilholzCharité Comprehensive Cancer Center, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Naveed IshaqueBerlin Institute of Health at Charité - Universitätsmedizin Berlin, Center of Digital Health, Berlin, Germany.
Sebastian StintzingDepartment of Hematology, Oncology, and Cancer Immunology, (CCM), Charité - Universitätsmedizin Berlin, Berlin, Germany.
Loredana VecchioneCharité Comprehensive Cancer Center, Charité - Universitätsmedizin Berlin, Berlin, Germany. loredana.vecchione@charite.de.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDrug resistance and lack of predicting biomarkers are a major challenge for cancer therapy. The combination of a BRAF inhibitor (BRAFi) together with an anti-EGFR inhibitor (EGFRi) represents a standard of care approach in BRAFV600E metastatic colorectal cancer (mCRC) patients. However, predictive biomarkers of sensitivity, that could support patient selection for treatment with this combination, are currently missing. Therefore, our goal is to identify those biomarkers associated with response to the combination of BRAFi and EGFRi.

methodsHere, we established a living biobank of BRAFV600E colorectal cancer patients derived organoids (PDOs) and categorized them as sensitive or resistant to the combination of BRAFi and EGFRi using short term proliferation assays. To elucidate biomarkers of response, drug testing was integrated with genomic, transcriptomic, proteomic and single-cell transcriptmic profiling of our PDOs.

resultsHere we revealed the PTEN/PIK3CA/p-AKT axis as mechanism of primary sensitivity while ROS pathway inhibition as driver for primary resistance. Finally, we newly discovered histology and cellular composition as biomarker of drug response.

conclusionThese data align with recently published clinical trial data, thus reinforcing the proof that PDOs can be used for biomarker identification. The use of histology and cellular compositions as biomarkers has to be further validated in clinical setting.

Indexed as

Biomarkers, TumorColonic NeoplasmsOrganoidsProtein Kinase InhibitorsProto-Oncogene Proteins B-rafDrug Resistance, NeoplasmErbB ReceptorsHumansMutationPTEN PhosphohydrolaseBiomarkers, TumorBRAF protein, humanEGFR protein, humanErbB ReceptorsProtein Kinase InhibitorsProto-Oncogene Proteins B-rafPTEN PhosphohydrolasePTEN protein, humanAKTBRAFBRAF V600E mutated Colorectal cancerDrug resistanceEncorafenib and cetuximabPatient derived organoidsPI3KPTENROS pathway

Identifiers

PMID41882736
PMCPMC13063721

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Registered trials

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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.