BRAF Mutant Gastrointestinal Stromal Tumor: First report of regression with BRAF inhibitor dabrafenib (GSK2118436) and whole exomic sequencing for analysis of acquired resistance

被引：117

作者：

Falchook, G. S. ^{[1
]}

Trent, J. C. ^{[2
]}

Heinrich, M. C. ^{[3
,4
]}

Beadling, C. ^{[3
,4
]}

Patterson, J. ^{[3
,4
]}

Bastida, C. C. ^{[1
]}

Blackman, S. C. ^{[5
]}

Kurzrock, R. ^{[6
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Div Canc Med, Dept Invest Canc Therapeut, Phase Clin Trials Program 1, Houston, TX 77030 USA

[2] Univ Miami, Sarcoma Med Oncol Program, Sylvester Comprehens Canc Ctr, Miami, FL USA

[3] Portland VA Med Ctr, Portland, OR USA

[4] Oregon Hlth & Sci Univ, Knight Canc Inst, Div Hematol & Oncol, Portland, OR 97201 USA

[5] GlaxoSmithKline, Collegeville, PA USA

[6] Univ Calif San Diego, Dept Med, Hematol Oncol Div, Moores Canc Ctr, San Diego, CA 92103 USA

来源：

ONCOTARGET | 2013年 / 4卷 / 02期

基金：

美国国家卫生研究院;

关键词：

Gastrointestinal stromal tumor; Dabrafenib; GSK2118436; BRAF mutation; BRAF inhibition; V600E; IMATINIB MESYLATE; PHASE-II; MUTATIONS; MELANOMA; GENE; PDGFRA;

D O I：

10.18632/oncotarget.864

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Activating oncogenic mutations of BRAF have been described in patients with gastrointestinal stromal tumor (GIST), but treatment of GIST with BRAF inhibitors and mechanisms of mediating the emergence of resistance in GIST have not been reported. Dabrafenib is a potent ATP-competitive inhibitor of BRAF kinase and is highly selective for mutant BRAF in kinase panel screening, cell lines, and xenografts. We report prolonged antitumor activity in the first patient with V600E BRAF-mutated GIST who was treated with a BRAF inhibitor. Whole exome sequencing performed in tumor tissue obtained at the time of progressive disease demonstrated a somatic gain-of-function PIK3CA mutation (H1047R) as well as a CDKN2A aberration, which may have contributed to eventual resistance to treatment.

引用

页码：310 / 315

页数：6

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