文章：

CRAF在癌症进展中的作用：从分子机制到精确治疗

The role of CRAF in cancer progression: from molecular mechanisms to precision therapies

原文发布日期：2024-01-09

DOI: 10.1038/s41568-023-00650-x

类型: Review Article

开放获取: 否

英文摘要：

The RAF family of kinases includes key activators of the pro-tumourigenic mitogen-activated protein kinase pathway. Hyperactivation of RAF proteins, particularly BRAF and CRAF, drives tumour progression and drug resistance in many types of cancer. Although BRAF is the most studied RAF protein, partially owing to its high mutation incidence in melanoma, the role of CRAF in tumourigenesis and drug resistance is becoming increasingly clinically relevant. Here, we summarize the main known regulatory mechanisms and gene alterations that contribute to CRAF activity, highlighting the different oncogenic roles of CRAF, and categorize RAF1 (CRAF) mutations according to the effect on kinase activity. Additionally, we emphasize the effect that CRAF alterations may have on drug resistance and how precision therapies could effectively target CRAF-dependent tumours. Here, we discuss preclinical and clinical findings that may lead to improved treatments for all types of oncogenic RAF1 alterations in cancer.

摘要翻译： 

RAF激酶家族是促肿瘤发生的有丝分裂原活化蛋白激酶通路的关键激活因子。RAF蛋白（尤其是BRAF和CRAF）的过度激活会驱动多种癌症的肿瘤进展和耐药性。尽管BRAF是研究最深入的RAF蛋白（部分原因在于其在黑色素瘤中的高突变率），但CRAF在肿瘤发生和耐药性中的作用正日益凸显临床意义。本文系统总结了已知调控CRAF活性的主要分子机制与基因改变，重点阐释CRAF的不同致癌作用，并根据对激酶活性的影响对RAF1（CRAF）突变进行分类。此外，我们着重分析了CRAF改变对耐药性的潜在影响，以及精准疗法如何有效靶向CRAF依赖性肿瘤。通过讨论临床前与临床研究进展，本文旨在为针对所有致癌性RAF1改变的癌症治疗策略提供优化方向。

原文链接：

The role of CRAF in cancer progression: from molecular mechanisms to precision therapies