Details

Autor(en) / Beteiligte

• Yokoyama, Daiju
• Hisamori, Shigeo
• Deguchi, Yasunori
• Nishigori, Tatsuto
• Okabe, Hiroshi
• Kanaya, Seiichiro
• Manaka, Dai
• Kadokawa, Yoshio
• Hata, Hiroaki
• Minamiguchi, Sachiko
• Tsunoda, Shigeru
• Obama, Kazutaka
• Sakai, Yoshiharu

Titel

PTEN is a predictive biomarker of trastuzumab resistance and prognostic factor in HER2-overexpressing gastroesophageal adenocarcinoma

Ist Teil von

• Scientific reports, 2021-04, Vol.11 (1), p.9013-9013, Article 9013

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2021

Quelle

EZB-FREE-00999 freely available EZB journals

Beschreibungen/Notizen

• 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.