Evidence map›Paper›PMID 32043788›Full record

ArticleThe oncologist2020

CIC Mutation as a Molecular Mechanism of Acquired Resistance to Combined BRAF-MEK Inhibition in Extramedullary Multiple Myeloma with Central Nervous System Involvement.

Matteo Claudio Da Vià, Antonio Giovanni Solimando, Andoni Garitano-Trojaola, Santiago Barrio, Umair Munawar, Susanne Strifler, Larissa Haertle, Nadine Rhodes, Eva Teufel, Cornelia Vogt and 5 more

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

Article in The oncologist, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed
3.5field-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.

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

43 citing papers in PubMed, 59 citations in OpenAlex.

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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

15 authors at 2 institutions in 2 countries.

Matteo Claudio Da ViàDepartment of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany.ORCID 0000-0002-5396-6584
Antonio Giovanni SolimandoDepartment of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany.ORCID 0000-0002-2293-9698
Andoni Garitano-TrojaolaDepartment of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany.ORCID 0000-0003-4710-6753
Santiago BarrioDepartment of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany.
Umair MunawarDepartment of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany.
Susanne StriflerDepartment of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany.
Larissa HaertleDepartment of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany.
Nadine RhodesDepartment of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany.
Eva TeufelDepartment of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany.
Cornelia VogtDepartment of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany.
Constantin LapaDepartment of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany.ORCID 0000-0001-7536-2207
Andreas BeilhackDepartment of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany.ORCID 0000-0002-3165-2648
Leo RascheDepartment of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany.ORCID 0000-0002-9536-9649
Hermann EinseleDepartment of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany.ORCID 0000-0002-7680-0819
K Martin KortümDepartment of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany.ORCID 0000-0002-7011-0286
Universitätsklinikum Würzburg · DEUniversity of Bari Aldo Moro · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Combined MEK-BRAF inhibition is a well-established treatment strategy in BRAF-mutated cancer, most prominently in malignant melanoma with durable responses being achieved through this targeted therapy. However, a subset of patients face primary unresponsiveness despite presence of the activating mutation at position V600E, and others acquire resistance under treatment. Underlying resistance mechanisms are largely unknown, and diagnostic tests to predict tumor response to BRAF-MEK inhibitor treatment are unavailable. Multiple myeloma represents the second most common hematologic malignancy, and point mutations in BRAF are detectable in about 10% of patients. Targeted inhibition has been successfully applied, with mixed responses observed in a substantial subset of patients mirroring the widespread spatial heterogeneity in this genomically complex disease. Central nervous system (CNS) involvement is an extremely rare, extramedullary form of multiple myeloma that can be diagnosed in less than 1% of patients. It is considered an ultimate high-risk feature, associated with unfavorable cytogenetics, and, even with intense treatment applied, survival is short, reaching less than 12 months in most cases. Here we not only describe the first patient with an extramedullary CNS relapse responding to targeted dabrafenib and trametinib treatment, we furthermore provide evidence that a point mutation within the capicua transcriptional repressor (CIC) gene mediated the acquired resistance in this patient. KEY POINTS: BRAF mutations constitute an attractive druggable target in multiple myeloma. This is the first genomic dissection of the central nervous system involvement in a multiple myeloma patient harboring a druggable BRAF

Indexed as

Multiple MyelomaProto-Oncogene Proteins B-rafAntineoplastic Combined Chemotherapy ProtocolsCentral Nervous SystemHumansMitogen-Activated Protein Kinase KinasesMutationNeoplasm Recurrence, LocalProtein Kinase InhibitorsBRAF protein, humanMitogen-Activated Protein Kinase KinasesProtein Kinase InhibitorsProto-Oncogene Proteins B-rafBRAF mutationCapicua transcriptional repressorDrug resistanceExtramedullary diseaseMultiple myeloma

Identifiers

PMID32043788
PMCPMC7011664
OpenAlexW2981222016

What OpenQuestion holds

Textmetadata
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.