Evidence map›Paper›PMID 29540830›Full record

ReviewOncogene2018

Classifying BRAF alterations in cancer: new rational therapeutic strategies for actionable mutations.

Matthew Dankner, April A N Rose, Shivshankari Rajkumar, Peter M Siegel, Ian R Watson

Abstract readReview
PubMed Publisher
In one paragraph

Review in Oncogene, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 286 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
286citing papers in PubMed, 7 pooled it
–field-weighted citation impact
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

286 citing papers in PubMed, 7 syntheses or guidelines pooled it.

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226 more citing papers are in PubMed but not listed here.

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

5 authors.

Matthew DanknerGoodman Cancer Research Centre, McGill University, Montreal, QC, Canada.
April A N RoseDepartment of Medicine, Division of Medical Oncology, University of Toronto, Toronto, ON, Canada.ORCID http://orcid.org/0000-0002-9845-4603
Shivshankari RajkumarGoodman Cancer Research Centre, McGill University, Montreal, QC, Canada.
Peter M SiegelGoodman Cancer Research Centre, McGill University, Montreal, QC, Canada.ORCID http://orcid.org/0000-0002-5568-6586
Ian R WatsonGoodman Cancer Research Centre, McGill University, Montreal, QC, Canada. ian.watson2@mcgill.ca.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The RAS-RAF-MEK-ERK signaling cascade is among the most frequently mutated pathways in human cancer. Approximately 50% of melanoma patients possess a druggable hotspot V600E/K mutation in the BRAF protein kinase. FDA-approved combination therapies of BRAF and MEK inhibitors are available that provide survival benefits to patients with a BRAF V600 mutation. Non-V600 BRAF mutants are found in many cancers, and are more prevalent than V600 mutations in certain tumor types. For example, between 50-80% of BRAF mutations in non-small cell lung cancer and 22-30% in colorectal cancer encode for non-V600 mutants. As next generation sequencing becomes increasingly used in clinical practice, oncologists are frequently identifying non-V600 BRAF mutations in their patient's tumors, but are uncertain of viable therapeutic options that could be employed for optimal treatment. From recent studies, a new classification system is emerging for BRAF mutations based on biochemical and signaling mechanisms associated with these mutants. Class I BRAF mutations affect amino acid V600 and signal as RAS-independent active monomers, class II mutations function as RAS-independent activated dimers, and class III mutations are kinase impaired but increase signaling through the MAPK pathway due to enhanced RAS binding and subsequent CRAF activation. These distinct classes of BRAF mutations predict response to targeted therapies and have important implications for future drug development. Herein, we discuss pre-clinical and clinical findings that may lead to improved treatments for all classes of BRAF mutant cancers.

Indexed as

MutationAntineoplastic AgentsCarcinoma, Non-Small-Cell LungColorectal NeoplasmsHumansLung NeoplasmsMAP Kinase Signaling SystemMelanomaMolecular Targeted TherapyNeoplasmsProtein DomainsProtein Kinase InhibitorsProto-Oncogene Proteins B-rafAntineoplastic AgentsBRAF protein, humanProtein Kinase InhibitorsProto-Oncogene Proteins B-raf

Identifiers

PMID29540830

What OpenQuestion holds

Textmetadata
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.