PTEN is a predictive biomarker of trastuzumab resistance and prognostic factor in HER2-overexpressing gastroesophageal adenocarcinoma
Abstract Poor trastuzumab (Tmab) response of patients with human epidermal growth factor receptor 2-overexpressing gastric or gastroesophageal junction adenocarcinoma (HER2-GEA) is associated with the inhibition of phosphatase and tensin homolog (PTEN) expression. In this multicenter, retrospective...
Guardado en:
| Autores principales: | , , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Nature Portfolio
2021
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/af698eef3b3f4acea1b3b7bfb6a09a48 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| Sumario: | Abstract Poor trastuzumab (Tmab) response of patients with human epidermal growth factor receptor 2-overexpressing gastric or gastroesophageal junction adenocarcinoma (HER2-GEA) is associated with the inhibition of phosphatase and tensin homolog (PTEN) expression. In this multicenter, retrospective observational study, pathological samples of patients with HER2-GEA receiving Tmab-combined chemotherapy were immunohistochemically analyzed for PTEN expression. The primary endpoints were disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). We assessed the effect of conventional chemotherapy and Tmab alone or combined with PI3K pathway inhibitors in vitro in HER2-GEA cells with or without PTEN expression. Twenty-nine and 116 patients were in the PTEN-loss and PTEN-positive groups, respectively. In patients with the target region, DCR was significantly lower in PTEN-loss patients than in PTEN-positive patients (67% and 87%, respectively, p = 0.049). The multivariate analysis demonstrated that PTEN loss was significantly associated with shorter PFS (HR = 1.63, p = 0.035) and OS (HR = 1.83, p = 0.022). PTEN knockdown did not affect the cytostatic effect of 5-FU and cisplatin, whereas Tmab combined with the PI3K/mTOR inhibitor NPV-BEZ235 suppressed PTEN-knockdown cell proliferation. In patients with HER2-GEA, PTEN loss is a predictive biomarker of Tmab resistance and prognostic factor. Molecular-targeted therapy with a PI3K/mTOR inhibitor would be effective for HER2-GEA with PTEN loss. |
|---|