MAPK-signaling inhibition as a genome-based precision medicine in refractory osteosarcoma.

Abstract

e22164 Background: MAPK signaling pathways are often dysregulated in tumors and GNAQ mutation enables constitutive downstream MAPK signaling. Inhibition of these pathways with RAF inhibitor, sorafenib was investigated on N of 1 trial design setting for refractory osteosarcoma patient. Methods: The subject of this study was 25-year old male patient with heavily treated metastatic osteosarcoma and no treatment option was available including systemic chemotherapy and radiotherapy at the moment of enrollment. The disease burden of the patient was lung, chest wall and axillary lymph nodes and progressed rapidly with clinical deterioration. Whole exome sequencing of the genomic DNA from peripheral blood mononucleated cells and formalin fixed paraffin embedded tissues of primary tumor and two metastatic tumors with usage of one lane of paired-end, 100bp reads on Illimuna Hiseq. Several novel somatic mutations including GNAQ were identified in metastatic tumors(AACR 2014) and sorafenib 800mg was administered on p...