Cargando…

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

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 (regoraf...

Descripción completa

Detalles Bibliográficos
Autores principales: Hasegawa, Hiroko, Taniguchi, Hiroya, Nakamura, Yoshiaki, Kato, Takeshi, Fujii, Satoshi, Ebi, Hiromichi, Shiozawa, Manabu, Yuki, Satoshi, Masuishi, Toshiki, Kato, Ken, Izawa, Naoki, Moriwaki, Toshikazu, Oki, Eiji, Kagawa, Yoshinori, Denda, Tadamichi, Nishina, Tomohiro, Tsuji, Akihito, Hara, Hiroki, Esaki, Taito, Nishida, Tomohiro, Kawakami, Hisato, Sakamoto, Yasutoshi, Miki, Izumi, Okamoto, Wataru, Yamazaki, Kentaro, Yoshino, Takayuki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780005/
https://www.ncbi.nlm.nih.gov/pubmed/33075166
http://dx.doi.org/10.1111/cas.14693
_version_ 1783631430707838976
author Hasegawa, Hiroko
Taniguchi, Hiroya
Nakamura, Yoshiaki
Kato, Takeshi
Fujii, Satoshi
Ebi, Hiromichi
Shiozawa, Manabu
Yuki, Satoshi
Masuishi, Toshiki
Kato, Ken
Izawa, Naoki
Moriwaki, Toshikazu
Oki, Eiji
Kagawa, Yoshinori
Denda, Tadamichi
Nishina, Tomohiro
Tsuji, Akihito
Hara, Hiroki
Esaki, Taito
Nishida, Tomohiro
Kawakami, Hisato
Sakamoto, Yasutoshi
Miki, Izumi
Okamoto, Wataru
Yamazaki, Kentaro
Yoshino, Takayuki
author_facet Hasegawa, Hiroko
Taniguchi, Hiroya
Nakamura, Yoshiaki
Kato, Takeshi
Fujii, Satoshi
Ebi, Hiromichi
Shiozawa, Manabu
Yuki, Satoshi
Masuishi, Toshiki
Kato, Ken
Izawa, Naoki
Moriwaki, Toshikazu
Oki, Eiji
Kagawa, Yoshinori
Denda, Tadamichi
Nishina, Tomohiro
Tsuji, Akihito
Hara, Hiroki
Esaki, Taito
Nishida, Tomohiro
Kawakami, Hisato
Sakamoto, Yasutoshi
Miki, Izumi
Okamoto, Wataru
Yamazaki, Kentaro
Yoshino, Takayuki
author_sort Hasegawa, Hiroko
collection PubMed
description 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.
format Online
Article
Text
id pubmed-7780005
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-77800052021-01-08 FMS‐like tyrosine kinase 3 (FLT3) amplification in patients with metastatic colorectal cancer Hasegawa, Hiroko Taniguchi, Hiroya Nakamura, Yoshiaki Kato, Takeshi Fujii, Satoshi Ebi, Hiromichi Shiozawa, Manabu Yuki, Satoshi Masuishi, Toshiki Kato, Ken Izawa, Naoki Moriwaki, Toshikazu Oki, Eiji Kagawa, Yoshinori Denda, Tadamichi Nishina, Tomohiro Tsuji, Akihito Hara, Hiroki Esaki, Taito Nishida, Tomohiro Kawakami, Hisato Sakamoto, Yasutoshi Miki, Izumi Okamoto, Wataru Yamazaki, Kentaro Yoshino, Takayuki Cancer Sci Clinical Research 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. John Wiley and Sons Inc. 2020-11-20 2021-01 /pmc/articles/PMC7780005/ /pubmed/33075166 http://dx.doi.org/10.1111/cas.14693 Text en © 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Clinical Research
Hasegawa, Hiroko
Taniguchi, Hiroya
Nakamura, Yoshiaki
Kato, Takeshi
Fujii, Satoshi
Ebi, Hiromichi
Shiozawa, Manabu
Yuki, Satoshi
Masuishi, Toshiki
Kato, Ken
Izawa, Naoki
Moriwaki, Toshikazu
Oki, Eiji
Kagawa, Yoshinori
Denda, Tadamichi
Nishina, Tomohiro
Tsuji, Akihito
Hara, Hiroki
Esaki, Taito
Nishida, Tomohiro
Kawakami, Hisato
Sakamoto, Yasutoshi
Miki, Izumi
Okamoto, Wataru
Yamazaki, Kentaro
Yoshino, Takayuki
FMS‐like tyrosine kinase 3 (FLT3) amplification in patients with metastatic colorectal cancer
title FMS‐like tyrosine kinase 3 (FLT3) amplification in patients with metastatic colorectal cancer
title_full FMS‐like tyrosine kinase 3 (FLT3) amplification in patients with metastatic colorectal cancer
title_fullStr FMS‐like tyrosine kinase 3 (FLT3) amplification in patients with metastatic colorectal cancer
title_full_unstemmed FMS‐like tyrosine kinase 3 (FLT3) amplification in patients with metastatic colorectal cancer
title_short FMS‐like tyrosine kinase 3 (FLT3) amplification in patients with metastatic colorectal cancer
title_sort fms‐like tyrosine kinase 3 (flt3) amplification in patients with metastatic colorectal cancer
topic Clinical Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780005/
https://www.ncbi.nlm.nih.gov/pubmed/33075166
http://dx.doi.org/10.1111/cas.14693
work_keys_str_mv AT hasegawahiroko fmsliketyrosinekinase3flt3amplificationinpatientswithmetastaticcolorectalcancer
AT taniguchihiroya fmsliketyrosinekinase3flt3amplificationinpatientswithmetastaticcolorectalcancer
AT nakamurayoshiaki fmsliketyrosinekinase3flt3amplificationinpatientswithmetastaticcolorectalcancer
AT katotakeshi fmsliketyrosinekinase3flt3amplificationinpatientswithmetastaticcolorectalcancer
AT fujiisatoshi fmsliketyrosinekinase3flt3amplificationinpatientswithmetastaticcolorectalcancer
AT ebihiromichi fmsliketyrosinekinase3flt3amplificationinpatientswithmetastaticcolorectalcancer
AT shiozawamanabu fmsliketyrosinekinase3flt3amplificationinpatientswithmetastaticcolorectalcancer
AT yukisatoshi fmsliketyrosinekinase3flt3amplificationinpatientswithmetastaticcolorectalcancer
AT masuishitoshiki fmsliketyrosinekinase3flt3amplificationinpatientswithmetastaticcolorectalcancer
AT katoken fmsliketyrosinekinase3flt3amplificationinpatientswithmetastaticcolorectalcancer
AT izawanaoki fmsliketyrosinekinase3flt3amplificationinpatientswithmetastaticcolorectalcancer
AT moriwakitoshikazu fmsliketyrosinekinase3flt3amplificationinpatientswithmetastaticcolorectalcancer
AT okieiji fmsliketyrosinekinase3flt3amplificationinpatientswithmetastaticcolorectalcancer
AT kagawayoshinori fmsliketyrosinekinase3flt3amplificationinpatientswithmetastaticcolorectalcancer
AT dendatadamichi fmsliketyrosinekinase3flt3amplificationinpatientswithmetastaticcolorectalcancer
AT nishinatomohiro fmsliketyrosinekinase3flt3amplificationinpatientswithmetastaticcolorectalcancer
AT tsujiakihito fmsliketyrosinekinase3flt3amplificationinpatientswithmetastaticcolorectalcancer
AT harahiroki fmsliketyrosinekinase3flt3amplificationinpatientswithmetastaticcolorectalcancer
AT esakitaito fmsliketyrosinekinase3flt3amplificationinpatientswithmetastaticcolorectalcancer
AT nishidatomohiro fmsliketyrosinekinase3flt3amplificationinpatientswithmetastaticcolorectalcancer
AT kawakamihisato fmsliketyrosinekinase3flt3amplificationinpatientswithmetastaticcolorectalcancer
AT sakamotoyasutoshi fmsliketyrosinekinase3flt3amplificationinpatientswithmetastaticcolorectalcancer
AT mikiizumi fmsliketyrosinekinase3flt3amplificationinpatientswithmetastaticcolorectalcancer
AT okamotowataru fmsliketyrosinekinase3flt3amplificationinpatientswithmetastaticcolorectalcancer
AT yamazakikentaro fmsliketyrosinekinase3flt3amplificationinpatientswithmetastaticcolorectalcancer
AT yoshinotakayuki fmsliketyrosinekinase3flt3amplificationinpatientswithmetastaticcolorectalcancer