The Second-generation ALK Inhibitor Alectinib Effectively Induces Apoptosis in Human Neuroblastoma Cells and Inhibits Tumor Growth in a TH-MYCN Transgenic Neuroblastoma Mouse Model

Overview

Journal Cancer Lett

Specialty Oncology

Date 2017 Apr 30

PMID 28455243

Citations 23

Authors

Jiaxiong Lu

Shan Guan

Yanling Zhao

Yang Yu

Sarah E Woodfield

Huiyuan Zhang

Kristine L Yang

Shayahati Bieerkehazhi

Lin Qi

Xiaonan Li

Jerry Gu

Xin Xu

Jingling Jin

Jodi A Muscal

Tianshu Yang

Guo-Tong Xu

Jianhua Yang

Affiliations

Soon will be listed here.

Abstract

Activating germline mutations of anaplastic lymphoma kinase (ALK) occur in most cases of hereditary neuroblastoma (NB) and the constitutively active kinase activity of ALK promotes cell proliferation and survival in NB. Therefore, ALK kinase is a potential therapeutic target for NB. In this study, we show that the novel ALK inhibitor alectinib effectively suppressed cell proliferation and induces apoptosis in NB cell lines with either wild-type ALK or mutated ALK (F1174L and D1091N) by blocking ALK-mediated PI3K/Akt/mTOR signaling. In addition, alectinib enhanced doxorubicin-induced cytotoxicity and apoptosis in NB cells. Furthermore, alectinib induced apoptosis in an orthotopic xenograft NB mouse model. Also, in the TH-MYCN transgenic mouse model, alectinib resulted in decreased tumor growth and prolonged survival time. These results indicate that alectinib may be a promising therapeutic agent for the treatment of NB.

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