BRAFV600E Mutations in High-Grade Colorectal Neuroendocrine Tumors May Predict Responsiveness to BRAF-MEK Combination Therapy.

Autor:	Klempner SJ; Division of Hematology-Oncology, Department of Medicine, Chao Family Comprehensive Cancer Center, University of California, Irvine, School of Medicine, Orange, California. sklempner@theangelesclinic.org., Gershenhorn B; Cancer Treatment Centers of America, Midwestern Regional Medical Center, Zion, Illinois., Tran P; Division of Hematology-Oncology, Department of Medicine, Chao Family Comprehensive Cancer Center, University of California, Irvine, School of Medicine, Orange, California., Lee TK; Department of Pathology, University of California, Irvine, Orange, California., Erlander MG; Trovagene, Inc., San Diego, California., Gowen K; Foundation Medicine, Inc., Cambridge, Massachusetts., Schrock AB; Foundation Medicine, Inc., Cambridge, Massachusetts., Morosini D; Foundation Medicine, Inc., Cambridge, Massachusetts., Ross JS; Foundation Medicine, Inc., Cambridge, Massachusetts. Albany Medical College, Albany, New York., Miller VA; Foundation Medicine, Inc., Cambridge, Massachusetts., Stephens PJ; Foundation Medicine, Inc., Cambridge, Massachusetts., Ou SH; Division of Hematology-Oncology, Department of Medicine, Chao Family Comprehensive Cancer Center, University of California, Irvine, School of Medicine, Orange, California., Ali SM; Foundation Medicine, Inc., Cambridge, Massachusetts.
Jazyk:	angličtina
Zdroj:	Cancer discovery [Cancer Discov] 2016 Jun; Vol. 6 (6), pp. 594-600. Date of Electronic Publication: 2016 Apr 05.
DOI:	10.1158/2159-8290.CD-15-1192
Abstrakt:	Unlabelled: Neuroendocrine tumors comprise a heterogeneous group of malignancies with a broad spectrum of clinical behavior. Poorly differentiated tumors follow an aggressive course with limited treatment options, and new approaches are needed. Oncogenic BRAF V600E (BRAF(V600E)) substitutions are observed primarily in melanoma, colon cancer, and non-small cell lung cancer, but have been identified in multiple tumor types. Here, we describe the first reported recurrent BRAF(V600E) mutations in advanced high-grade colorectal neuroendocrine tumors and identify a BRAF alteration frequency of 9% in 108 cases. Among these BRAF alterations, 80% were BRAF(V600E) Dramatic response to BRAF-MEK combination therapy occurred in two cases of metastatic high-grade rectal neuroendocrine carcinoma refractory to standard therapy. Urinary BRAF(V600E) circulating tumor DNA monitoring paralleled disease response. Our series represents the largest study of genomic profiling in colorectal neuroendocrine tumors and provides strong evidence that BRAF(V600E) is an oncogenic driver responsive to BRAF-MEK combination therapy in this molecular subset. Significance: BRAF(V600E) is an established oncogenic driver, but significant disparities in response exist among tumor types. Two patients with treatment-refractory high-grade colorectal neuroendocrine tumors harboring BRAF(V600E) exhibited rapid and durable response to combined BRAF-MEK inhibition, providing the first clinical evidence of efficacy in this aggressive tumor type. Cancer Discov; 6(6); 594-600. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 561. Competing Interests: KG, AS, JR, VAM, PJS, and SMA are stockholders and employees of Foundation Medicine. MGE is a stockholder and employee of Trovagene. The remaining authors have no potential conflicts of interest to disclose. (©2016 American Association for Cancer Research.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu