Remarkable Response to Sorafenib in Advanced Lung Adenocarcinoma and Oncogenic ARAF Mutation

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As reported in Journal of Clinical Investigation by Imielinski and colleagues, whole-genome and RNA sequencing of tumor and normal tissue in a patient with advanced lung adenocarcinoma who exhibited a remarkable response to sorafenib (Nexavar) revealed a somatic ARAF S214 mutation expressed at high levels in tumor. The patient had exhibited near-complete clinical and radiographic remission for 5 years.

The investigators identified additional mutations affecting this residue of ARAF and a nearby residue in the related kinase RAF1 across 1% of an independent cohort of lung adenocarcinomas. The ARAF mutations were found to transform immortalized human airway epithelial cells in a sorafenib-sensitive manner.

As stated by the investigators, “These results suggest that mutant ARAF is an oncogenic driver in lung adenocarcinoma and an indicator of sorafenib response.” ■

Imielinski M, et al: J Clin Invest 124:1582-1586, 2014.




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