Πέμπτη 30 Ιανουαρίου 2020

Stathmin guides personalized therapy in oral squamous cell carcinoma.

Stathmin guides personalized therapy in oral squamous cell carcinoma.:

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Stathmin guides personalized therapy in oral squamous cell carcinoma.

Cancer Sci. 2020 Jan 28;:

Authors: Ju WT, Ma HL, Zhao TC, Liang SY, Zhu DW, Wang LZ, Li J, Zhang ZY, Zhou G, Zhong LP

Abstract

The survival benefit from docetaxel, cisplatin, and 5- fluorouracil (TPF) induction chemotherapy in oral squamous cell carcinoma (OSCC) patients is not satisfactory. Previously, we identified stathmin, a microtubule-destabilizing protein, is overexpressed in OSCC. Here we further investigate its role as a biomarker that impacts on OSCC chemosensitivity. We analyzed the predictive value of stathmin on TPF induction chemotherapy and its impact on OSCC cell chemosensitivity. Then we further investigated the therapeutic effects of the combination therapy of TPF chemotherapy and PI3K-AKT-mTOR inhibitors in vitro and in vivo. We found OSCC patients with low stathmin expression benefited from TPF induction chemotherapy, while OSCC patients with high stathmin expression could not benefit from TPF induction chemotherapy. Stathmin overexpression promoted cellular proliferation and decreased OSCC cell sensitivity to TPF treatment. Additionally, inhibition of PI3K-AKT-mTOR signaling pathway decreased stathmin expression and phosphorylation. The combination therapy of TPF chemotherapy and PI3K-AKT-mTOR inhibitors exhibited potent anti-tumor effect both in vitro and in vivo. Therefore, stathmin can be used as a predictive biomarker for TPF induction chemotherapy and combination therapy regimen based on stathmin expression might improve the survival of OSCC patients.

PMID: 31994271 [PubMed - as supplied by publisher]

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