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Cancer Chemotherapy and Pharmacology
Published in: Cancer Chemotherapy and Pharmacology 4/2019

01-10-2019 | NSCLC | Review Article

Resistance mechanisms and potent-targeted therapies of ROS1-positive lung cancer

Authors: Annie Roys, Xing Chang, Yang Liu, Xiaobo Xu, Yingliang Wu, Daiying Zuo

Published in: Cancer Chemotherapy and Pharmacology | Issue 4/2019

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Abstract

The discovery of targetable mutations, which cause gene rearrangement, led to a major advancement in the treatment of patients with non-small cell lung cancer (NSCLC), and cancers with such mutations can be paired with drugs which specifically target them. c-ros oncogene (ROS1) positive NSCLC is one molecular subtype of NSCLC with a therapeutic target. Currently, different targeted therapies and ROS1 inhibitors have been discovered, but all are in different investigational phases, with only one (crizotinib) which is FDA approved. Crizotinib is a small-molecule tyrosine kinase inhibitor (TKI) which was discovered to actively inhibit ALK, MET, and ROS1. Crizotinib has shown to be remarkably efficacious against ROS1 lung cancer, prompting ROS1 detection in lung cancer to be quite significant. Sadly, crizotinib resistance in ROS1 is a frequent occurrence which poses a major clinical challenge in the successful treatment of ROS1 lung cancer; hence, the discovery of the second and third generation ROS1 inhibitors is of utmost importance. In this review, we discuss the underlying mechanisms through which ROS1 tumor cells acquire resistance to crizotinib—the first-line drug for ROS1-positive NSCLC, and summarize various new potent drugs which can overcome this resistance and serve as viable alternatives.
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Metadata
Title
Resistance mechanisms and potent-targeted therapies of ROS1-positive lung cancer
Authors
Annie Roys
Xing Chang
Yang Liu
Xiaobo Xu
Yingliang Wu
Daiying Zuo
Publication date
01-10-2019
Publisher
Springer Berlin Heidelberg
Published in
Cancer Chemotherapy and Pharmacology / Issue 4/2019
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-019-03902-6

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