FMS‐like tyrosine kinase 3 ( FLT3 ) amplification in patients with metastatic colorectal cancer

Autor: Hisato Kawakami, Hiroko Hasegawa, Ken Kato, Hiroki Hara, Tomohiro Nishina, Naoki Izawa, Tadamichi Denda, Yoshinori Kagawa, Akihito Tsuji, Yoshiaki Nakamura, Izumi Miki, Toshikazu Moriwaki, Yasutoshi Sakamoto, Kentaro Yamazaki, Eiji Oki, Takeshi Kato, Tomohiro Nishida, Satoshi Yuki, Hiromichi Ebi, Wataru Okamoto, Satoshi Fujii, Toshiki Masuishi, Manabu Shiozawa, Takayuki Yoshino, Hiroya Taniguchi, Taito Esaki
Rok vydání: 2020
Předmět:
Male
0301 basic medicine
Oncology
Cancer Research
Pyridines
Colorectal cancer
next‐generation sequencing
chemistry.chemical_compound
fluids and secretions
0302 clinical medicine
hemic and lymphatic diseases
Aged
80 and over
FLT3 amplification
hemic and immune systems
General Medicine
Middle Aged
Treatment efficacy
Haematopoiesis
Treatment Outcome
030220 oncology & carcinogenesis
embryonic structures
Original Article
Female
Colorectal Neoplasms
Adult
medicine.medical_specialty
colorectal cancer
Antineoplastic Agents
Adenocarcinoma
Young Adult
03 medical and health sciences
Clinical Research
Cancer genome
Internal medicine
Regorafenib
medicine
Humans
In patient
Gene
Aged
Retrospective Studies
business.industry
Phenylurea Compounds
copy number status
Gene Amplification
medicine.disease
030104 developmental biology
fms-Like Tyrosine Kinase 3
chemistry
Fms-Like Tyrosine Kinase 3
prognosis
business
Zdroj: Cancer Science
ISSN: 1349-7006
1347-9032
Popis: FMS‐like tyrosine kinase 3 (FLT3) plays a key role in hematopoiesis. However, the oncogenic role of FLT3 amplification in patients with metastatic colorectal cancer (mCRC) remains unclear. Here, we aimed to evaluate the characteristics, prognosis, and treatment efficacy of an FLT3 inhibitor (regorafenib) in patients with mCRC with FLT3 amplifications. Tumor tissue samples from 2329 patients were sequenced using NGS in the Nationwide Cancer Genome Screening Project in Japan. The effects of clinicopathological features, co‐altered genes, prognosis, and efficacy of regorafenib were investigated. Between April 2015 and June 2018, 85 patients with mCRC with FLT3 amplification were observed. There were no differences in baseline characteristics between patients with or without FLT3 amplification. The frequency of RAS or other gene co‐alterations was inversely correlated with the copy number status. Median survival time in patients with FLT3 amplification was significantly shorter compared with those with non‐FLT3 amplification. Further investigations of FLT3 amplification as a potential treatment target in mCRC are warranted.
High FLT3 amplification may function not only as a prognostic factor but a promising treatment target in metastatic colorectal cancer.
Databáze: OpenAIRE
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