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

•The computational simulation model may be useful for predicting therapeutic effectiveness to BRAF compound mutations.•In addition to the generation of genomic information, the construction of a simulation database is important for establishing personalized medicine, helping prevent missing appropri...

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Veröffentlicht in:Cancer genetics 2022-08, Vol.266-267, p.1-6
Hauptverfasser: Seto, Katsutoshi, Shimizu, Junichi, Masago, Katsuhiro, Araki, Mitsugu, Katayama, Ryohei, Sagae, Yukari, Fujita, Shiro, Horio, Yoshitsugu, Sasaki, Eiichi, Kuroda, Hiroaki, Okubo, Kenichi, Okuno, Yasushi, Hida, Toyoaki
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Sprache:eng
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Zusammenfassung:•The computational simulation model may be useful for predicting therapeutic effectiveness to BRAF compound mutations.•In addition to the generation of genomic information, the construction of a simulation database is important for establishing personalized medicine, helping prevent missing appropriate therapeutic opportunities in patients with druggable driver mutations. 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.
ISSN:2210-7762
2210-7770
DOI:10.1016/j.cancergen.2022.05.001