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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 Cancer genetics
Vol 266-267
Issue
Date 2022 08
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, May 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