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Ref Type Journal Article
PMID (34158345)
Authors Kano H, Ichihara E, Watanabe H, Nishii K, Ando C, Nakasuka T, Ninomiya K, Kato Y, Kubo T, Rai K, Ohashi K, Hotta K, Tabata M, Maeda Y, Kiura K
Title SHP2 Inhibition Enhances the Effects of Tyrosine Kinase Inhibitors in Preclinical Models of Treatment-naïve ALK-, ROS1- , or EGFR -altered Non-small Cell Lung Cancer.
Journal Vol Issue Date Pages Journal Short Title
Molecular cancer therapeutics 20 9 2021 Sep 1653-1662 Mol Cancer Ther
URL
Abstract Text After molecular-targeted therapy, some cancer cells may remain that are resistant to therapies targeting oncogene alterations, such as those in the genes encoding the EGFR and anaplastic lymphoma kinase ( ALK ) as well as c-ros oncogene 1 ( ROS1 ). The mechanisms underlying this type of resistance are unknown. In this article, we report the potential role of Src homology 2 domain-containing phosphatase 2 (SHP2) in the residual cells of ALK / ROS1 / EGFR- altered non-small cell lung cancer (NSCLC). Molecular-targeted therapies failed to inhibit the ERK signaling pathway in the residual cells, whereas the SHP2 inhibitor SHP099 abolished their remaining ERK activity. SHP099 administered in combination with molecular-targeted therapy resulted in marked growth inhibition of cancer cells both in vitro and in vivo Thus, treatment combining an SHP2 inhibitor and a tyrosine kinase inhibitor may be a promising therapeutic strategy for oncogene-driven NSCLC.

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