蛋白激酶C-α（PKC-α）在胃肠道恶性肿瘤中的作用。

The role of protein kinase C-alpha (PKC-alpha) in malignancies of the gastrointestinal tract.

作者信息

Lahn M, Paterson B M, Sundell K, Ma D

机构信息

Divison of Oncology Product Development, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.

出版信息

Eur J Cancer. 2004 Jan;40(1):10-20. doi: 10.1016/j.ejca.2003.08.020.

DOI:10.1016/j.ejca.2003.08.020

PMID:14687784

Abstract

Drugs specifically designed to block cellular signalling proteins are currently evaluated as a new way to treat gastrointestinal tumours. One such "new targeted agent" is aprinocarsen, an antisense oligonucleotide that specifically blocks the mRNA of protein kinase C-alpha (PKC-alpha). Blocking PKC-alpha, an important cellular signalling molecule associated with tumour growth, is anticipated to result in tumour cell arrest and achieve clinical benefits. However, it is not known which patients may benefit most from a specific inhibition of PKC-alpha. Past experience with other novel targeted agents suggests that expression of the target molecule is an important factor for the success of such a specific therapy. Therefore, reviewing the specific role of PKC-alpha in various gastrointestinal tumours may contribute to focus the clinical development of selective or specific PKC-alpha inhibitors, such as aprinocarsen, on those patients with a distinctive PKC-alpha expression pattern.

摘要

目前，专门设计用于阻断细胞信号蛋白的药物正作为治疗胃肠道肿瘤的一种新方法进行评估。一种这样的“新型靶向药物”是阿普瑞司他，一种反义寡核苷酸，它能特异性地阻断蛋白激酶C-α（PKC-α）的信使核糖核酸（mRNA）。阻断PKC-α（一种与肿瘤生长相关的重要细胞信号分子）有望导致肿瘤细胞停滞并实现临床获益。然而，尚不清楚哪些患者可能从PKC-α的特异性抑制中获益最多。过去使用其他新型靶向药物的经验表明，靶分子的表达是这种特异性治疗成功的一个重要因素。因此，回顾PKC-α在各种胃肠道肿瘤中的具体作用，可能有助于将选择性或特异性PKC-α抑制剂（如阿普瑞司他）的临床开发聚焦于那些具有独特PKC-α表达模式的患者。