期刊
BRITISH JOURNAL OF CANCER
卷 117, 期 10, 页码 1450-1458出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/bjc.2017.308
关键词
BRAF(V600E) mutation; BRAF(non-V600E) mutation; RAS mutation; metastatic colorectal cancer; anti-epidermal growth factor receptor monoclonal antibody
类别
资金
- Adaptable and Seamless Technology Transfer Program (ASTEP) through target-driven R&D, Practical Application Development by SME Start-up
- Japan Science and Technology Agency (JST)
- National Cancer Center Research and Development Fund [23-A-2]
- G & G Science Co., Ltd.
- Medical & Biological Laboratories Co., Ltd.
- Grants-in-Aid for Scientific Research [16K14619] Funding Source: KAKEN
Background: Patients with BRAF(V600E)-mutated metastatic colorectal cancer (mCRC) have a poorer prognosis as well as resistance to anti-EGFR antibodies. However, it is unclear whether BRAF mutations other than BRAF(V600E) (BRAF(non-V600E) mutations) contribute to anti-EGFR antibody resistance. Methods: This study was composed of exploratory and inference cohorts. Candidate biomarkers identified by whole exome sequencing from super-responders and nonresponders in the exploratory cohort were validated by targeted resequencing for patients who received anti-EGFR antibody in the inference cohort. Results: In the exploratory cohort, 31 candidate biomarkers, including KRAS/NRAS/BRAF mutations, were identified. Targeted resequencing of 150 patients in the inference cohort revealed 40 patients with RAS (26.7%), 9 patients with BRAF(V600E) (6.0%), and 7 patients with BRAF(non-V600E) mutations (4.7%), respectively. The response rates in RAS, BRAF(V600E), and BRAF(non-V600E) were lower than those in RAS/BRAF wild-type (2.5%, 0%, and 0% vs 31.9%). The median PFS in BRAF(non-V600E) mutations was 2.4 months, similar to that in RAS or BRAF(V600E) mutations (2.1 and 1.6 months) but significantly worse than that in wild-type RAS/BRAF (5.9 months). Conclusions: Although BRAF(non-V600E) mutations identified were a rare and unestablished molecular subtype, certain BRAF(non-V600E) mutations might contribute to a lesser benefit of anti-EGFR monoclonal antibody treatment.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据