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.
Mol Cancer Ther
; 20(9): 1653-1662, 2021 09.
Article
em En
| MEDLINE
| ID: mdl-34158345
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Piperidinas
/
Pirimidinas
/
Proteínas Tirosina Quinases
/
Proteínas Proto-Oncogênicas
/
Carcinoma Pulmonar de Células não Pequenas
/
Inibidores de Proteínas Quinases
/
Proteína Tirosina Fosfatase não Receptora Tipo 11
/
Quinase do Linfoma Anaplásico
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Mol Cancer Ther
Ano de publicação:
2021
Tipo de documento:
Article