Response to Anti-EGFR Therapy in Patients with BRAF non-V600-Mutant Metastatic Colorectal Cancer.


Journal

Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500

Informations de publication

Date de publication:
01 12 2019
Historique:
received: 18 06 2019
revised: 14 08 2019
accepted: 15 08 2019
pubmed: 14 9 2019
medline: 22 9 2020
entrez: 14 9 2019
Statut: ppublish

Résumé

While mutations in BRAF in metastatic colorectal cancer (mCRC) most commonly occur at the V600 amino acid, with the advent of next-generation sequencing, non-V600 BRAF mutations are increasingly identified in clinical practice. It is unclear whether these mutants, like BRAF V600E, confer resistance to anti-EGFR therapy. We conducted a multicenter pooled analysis of consecutive patients with non-V600 BRAF-mutated mCRCs identified between 2010 and 2017. Non-V600 BRAF mutations were divided into functional classes based on signaling mechanism and kinase activity: activating and RAS-independent (class 2) or kinase-impaired and RAS-dependent (class 3). Forty patients with oncogenic non-V600 BRAF-mutant mCRC received anti-EGFR antibody treatment [ Response to EGFR antibody treatment in mCRCs with class 2 BRAF mutants is rare, while a large portion of CRCs with class 3 BRAF mutants respond. Patients with colorectal cancer with class 3 BRAF mutations should be considered for anti-EGFR antibody treatment.

Identifiants

pubmed: 31515458
pii: 1078-0432.CCR-19-2004
doi: 10.1158/1078-0432.CCR-19-2004
pmc: PMC6891165
mid: NIHMS1538023
doi:

Substances chimiques

Protein Kinase Inhibitors 0
EGFR protein, human EC 2.7.10.1
ErbB Receptors EC 2.7.10.1
BRAF protein, human EC 2.7.11.1
Proto-Oncogene Proteins B-raf EC 2.7.11.1
Cetuximab PQX0D8J21J

Types de publication

Journal Article Multicenter Study Randomized Controlled Trial Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

7089-7097

Subventions

Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA233736
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA210085
Pays : United States
Organisme : NIH HHS
ID : U54 OD020355
Pays : United States

Commentaires et corrections

Type : CommentIn

Informations de copyright

©2019 American Association for Cancer Research.

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Auteurs

Rona Yaeger (R)

Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.

Daisuke Kotani (D)

Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.

Sebastián Mondaca (S)

Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.

Aparna R Parikh (AR)

Massachusetts General Hospital Cancer Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts.

Hideaki Bando (H)

Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan.

Emily E Van Seventer (EE)

Massachusetts General Hospital Cancer Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts.

Hiroya Taniguchi (H)

Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.

HuiYong Zhao (H)

Department of Molecular Pharmacology and Chemistry, Memorial Sloan Kettering Cancer Center, New York, New York.

Claire N Thant (CN)

Program in Molecular Pharmacology, Memorial Sloan Kettering Cancer Center, New York, New York.

Elisa de Stanchina (E)

Department of Molecular Pharmacology and Chemistry, Memorial Sloan Kettering Cancer Center, New York, New York.

Neal Rosen (N)

Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
Program in Molecular Pharmacology, Memorial Sloan Kettering Cancer Center, New York, New York.

Ryan B Corcoran (RB)

Massachusetts General Hospital Cancer Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts.

Takayuki Yoshino (T)

Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.

Zhan Yao (Z)

Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
Program in Molecular Pharmacology, Memorial Sloan Kettering Cancer Center, New York, New York.

Hiromichi Ebi (H)

Division of Molecular Therapeutics, Aichi Cancer Center Research Institute, Nagoya, Aichi, Japan. hebi@aichi-cc.jp.
Division of Advanced Cancer Therapeutics, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.

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Classifications MeSH