Reference Detail

Ref Type

PMID

(38766698)

Authors

Tamura A, Inaba Higashiyama R, Yoshida T, Satozono Y, Ohe Y

Title

Response to dabrafenib plus trametinib on a rare BRAF mutation (V600_W604 deletion-insertion R) in an advanced non-small cell lung cancer patient.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Thoracic cancer			2024 May 20		Thorac Cancer

URL

Abstract Text

Although dabrafenib plus trametinib has been approved for BRAF V600E mutation positive advanced non-small cell lung cancer (NSCLC), data on its efficacy against uncommon BRAF mutations are still limited due to their rare frequency. We report a case of 70-year-old woman with BRAF V600_W604 deletion-insertion R-positive stage IVA lung adenocarcinoma, who was successfully treated with dabrafenib plus trametinib. Herein, we discuss the oncogenic role of uncommon BRAF mutations and highlight the importance of performing comprehensive genomic profiling on patients without any targetable gene alterations in companion diagnostics.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance
BRAF	V600_W604delinsR	indel	unknown	BRAF V600_W604delinsR results in the deletion of five amino acids in the protein kinase domain of the Braf protein from amino acids 600 to 604, combined with the insertion of an arginine (R) at the same site (UniProt.org). V600_W604delinsR has been identified in the scientific literature (PMID: 38766698, PMID: 30442523), but has not been biochemically characterized, and therefore, its effect on Braf protein function is unknown (PubMed, May 2024).

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
BRAF V600_W604delinsR	lung adenocarcinoma	predicted - sensitive	Dabrafenib + Trametinib	Case Reports/Case Series	Actionable	In a clinical case study, treatment with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in a partial response after 48 days, shrinkage of metastatic lesions, and decreased pleural effusion in a patient with advanced lung adenocarcinoma harboring BRAF V600_W604delinsR (PMID: 38766698).	38766698