当前位置: X-MOL 学术Expert Opin. Biol. Ther. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
KRAS mutations in metastatic colorectal cancer: from a de facto ban on anti-EGFR treatment in the past to a potential biomarker for precision medicine
Expert Opinion on Biological Therapy ( IF 4.6 ) Pub Date : 2021-08-18 , DOI: 10.1080/14712598.2021.1967318
Dahna Coupez 1 , Pauline Hulo 1 , Yann Touchefeu 1, 2 , Marc G Denis 3 , Jaafar Bennouna 4
Affiliation  

ABSTRACT

Introduction

The high frequency of RAS mutations, particularly KRAS mutations, in colorectal cancer (CRC) and the ineffectiveness of anti-EGFR antibodies in treating this disease has created a significant unmet medical need, especially for treating patients in the metastatic phase of this disease. There are many different types of RAS mutations, the most frequent being G12V (c.35 G > T (p.G12V)), G12D (c.35 G > A (p.G12D)), and G13D (c.38 G > A (p.G13D)). Here, we provide an overview of RAS mutations in CRC and their therapeutic implications.

Areas covered

The therapeutic strategies against metastatic CRC with RAS mutations are elaborated according to patient and disease characteristics and integrated into a multiline strategy. The complexity of the molecular structure of RAS and its relationship with the MAPK/ERK pathway partly explain the initial therapeutic failure with MEK or farnesyltransferase inhibitors. Conversely, the development of direct KRAS inhibitors or drugs targeting RAS regulators (e.g. SOS1 and SHP2) has opened new therapeutic fields, requiring the distinction of each KRAS mutation type.

Expert Opinion

In the future, KRAS inhibitors, including SOS1 and SHP2 inhibitors, might be used in combination with other signal transduction inhibitors, such as MEK inhibitors or anti-EGFR antibodies, which block alternative pathways of activation.



中文翻译:

转移性结直肠癌中的 KRAS 突变:从过去事实上禁止抗 EGFR 治疗到精准医学的潜在生物标志物

摘要

介绍

结直肠癌 (CRC) 中RAS突变的高频率,特别是KRAS突变,以及抗 EGFR 抗体在治疗该疾病中的无效性,已经产生了巨大的未满足的医疗需求,特别是对于治疗处于该疾病转移期的患者。有许多不同类型的RAS突变,最常见的是 G12V (c.35 G > T (p.G12V))、G12D (c.35 G > A (p.G12D)) 和 G13D (c.38 G > A (p.G13D))。在这里,我们概述了 CRC 中的RAS突变及其治疗意义。

涵盖的领域

针对具有RAS突变的转移性 CRC 的治疗策略根据患者和疾病特征进行了详细阐述,并整合到多线策略中。RAS 分子结构的复杂性及其与 MAPK/ERK 通路的关系部分解释了 MEK 或法尼基转移酶抑制剂最初的治疗失败。相反,直接 KRAS 抑制剂或靶向 RAS 调节剂(例如 SOS1 和 SHP2)的药物的开发开辟了新的治疗领域,需要区分每种KRAS突变类型。

专家意见

未来,KRAS 抑制剂,包括 SOS1 和 SHP2 抑制剂,可能会与其他信号转导抑制剂联合使用,例如 MEK 抑制剂或抗 EGFR 抗体,它们会阻断替代的激活途径。

更新日期:2021-09-21
down
wechat
bug