Evidence map›Paper›PMID 27048246›Full record

ArticleCancer discovery2016

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

Samuel J Klempner, Bruce Gershenhorn, Phu Tran, Thomas K Lee, Mark G Erlander, Kyle Gowen, Alexa B Schrock, Deborah Morosini, Jeffrey S Ross, Vincent A Miller and 3 more

Open access · bronzeAbstract readCase Reports
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer discovery, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed
7.4field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

53 citing papers in PubMed, 84 citations in OpenAlex.

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  7. Rectal neuroendocrine tumors: Update.World journal of gastrointestinal oncology · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 5 institutions in 1 country.

Samuel J KlempnerDivision of Hematology-Oncology, Department of Medicine, Chao Family Comprehensive Cancer Center, University of California, Irvine, School of Medicine, Orange, California. sklempner@theangelesclinic.org.
Bruce GershenhornCancer Treatment Centers of America, Midwestern Regional Medical Center, Zion, Illinois.
Phu TranDivision of Hematology-Oncology, Department of Medicine, Chao Family Comprehensive Cancer Center, University of California, Irvine, School of Medicine, Orange, California.
Thomas K LeeDepartment of Pathology, University of California, Irvine, Orange, California.
Mark G ErlanderTrovagene, Inc., San Diego, California.
Kyle GowenFoundation Medicine, Inc., Cambridge, Massachusetts.
Alexa B SchrockFoundation Medicine, Inc., Cambridge, Massachusetts.
Deborah MorosiniFoundation Medicine, Inc., Cambridge, Massachusetts.
Jeffrey S RossFoundation Medicine, Inc., Cambridge, Massachusetts. Albany Medical College, Albany, New York.
Vincent A MillerFoundation Medicine, Inc., Cambridge, Massachusetts.
Philip J StephensFoundation Medicine, Inc., Cambridge, Massachusetts.
Sai-Hong Ignatius OuDivision of Hematology-Oncology, Department of Medicine, Chao Family Comprehensive Cancer Center, University of California, Irvine, School of Medicine, Orange, California.
Siraj M AliFoundation Medicine, Inc., Cambridge, Massachusetts.
GlobalFoundries (United States) · USUniversity of California, Irvine Medical Center · USCancer Treatment Centers of America · USUniversity of California, Irvine · USWorkplace Technologies Research · US

Funding

Univ.of Calif., Irvine Cancer Center Support GrantP30CA062203 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI Christine Hui · 1994 to 2026
$57.9M
NCI NIH HHS P30 CA062203
6 · The paper itself

Abstract

unlabelledNeuroendocrine 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.

Indexed as

MutationAdultAgedAmino Acid SubstitutionAntineoplastic Combined Chemotherapy ProtocolsBiopsyCodonColorectal NeoplasmsFemaleHumansMolecular Targeted TherapyNeoplasm GradingNeoplasm MetastasisNeuroendocrine TumorsPositron Emission Tomography Computed TomographyProtein Kinase InhibitorsCodonProtein Kinase InhibitorsProto-Oncogene Proteins B-raf

Identifiers

PMID27048246
PMCPMC5008024
OpenAlexW2315581823

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.