Copy Number Changes Are Associated with Response to Treatment with Carboplatin, Paclitaxel, and Sorafenib in Melanoma

作者: Melissa A. Wilson , Fengmin Zhao , Sanika Khare , Jason Roszik , Scott E. Woodman

DOI: 10.1158/1078-0432.CCR-15-1162

关键词: V600EBiologyBioinformaticsInternal medicineOncologyMelanomaKRASCarboplatinCancerMutationPaclitaxelSorafenib

摘要: Purpose: Copy number alterations have been shown to be involved in melanoma pathogenesis. The randomized phase III clinical trial E2603: carboplatin, paclitaxel, ± sorafenib (CP vs. CPS) offers a large collection of tumor samples evaluate association somatic mutations, genomic alterations, and outcomes, prior current FDA-approved therapies. Experimental Design: mutational analysis on 119 pretreatment was performed. Results: CPS therapy associated with improved progression-free survival (PFS) compared CP patients tumors RAF1 (cRAF) gene copy gains (HR, 0.372; P = 0.025) or CCND1 0.45; 0.035). overall (OS) KRAS 0.25; BRAF gain MET amplification were more common V600K versus V600E mutations (P Conclusions: We observed treatment response whose (cRAF), KRAS, amplification, all which can attributed targeting CRAF. These should incorporated future studies for evaluation as biomarkers. Clin Cancer Res; 22(2); 374–82. ©2015 AACR.

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