Reference Detail

Ref Type

Journal Article

PMID

(35598548)

Authors

Seto K, Shimizu J, Masago K, Araki M, Katayama R, Sagae Y, Fujita S, Horio Y, Sasaki E, Kuroda H, Okubo K, Okuno Y, Hida T

Title

Sensitivity to dabrafenib and trametinib treatments in patients with non-small-cell cancer harboring BRAF compound mutations: A pooled analysis of BRAF p.V600E-positive advanced non-small-cell lung cancer.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Cancer genetics	266-267		2022 08	1-6	Cancer Genet

URL

Abstract Text

The present study clarified the sensitivity of the BRAF tyrosine kinase inhibitor mechanism in patients with BRAF compound mutation and predicted the sensitivity using molecular dynamics simulation.We examined 16 BRAF tumors with p.V600E-positive non-small-cell lung cancer.One patient (6.2%) had a BRAF p.V600E and p.K601_W604 compound mutation with a good clinical response to dabrafenib and trametinib. Molecular dynamics simulation also complemented the effect.The combination of a genetic analysis and computational simulation model may help predict the sensitivity for dabrafenib in cases with a rare BRAF compound mutation. The construction of a genomic and simulation fused database is important for the development of personalized medicine in this field.

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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	K601_W604del	deletion	unknown	BRAF K601_W604del results in the deletion of four amino acids in the protein kinase domain of the Braf protein from amino acids 601 to 604 (UniProt.org). K601_W604del has been identified in the scientific literature (PMID: 35598548), but has not been biochemically characterized and therefore, its effect on Braf protein function is unknown (PubMed, Dec 2023).

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
BRAF V600E BRAF K601_W604del	lung non-small cell carcinoma	predicted - sensitive	Dabrafenib + Trametinib	Case Reports/Case Series	Actionable	In a clinical case study, third-line Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy resulted in a partial response and progression-free survival of 155 days in a non-small cell lung cancer patient harboring BRAF V600E and K601_W604del (PMID: 35598548).	35598548