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利用生物制剂靶向“不可成药的”RAS

Targeting the "undruggable" RAS with biologics.

作者信息

Whaby Michael, Khan Imran, O'Bryan John P

机构信息

Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, United States.

Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, United States; Ralph H. Johnson VA Medical Center, Charleston, SC, United States.

出版信息

Adv Cancer Res. 2022;153:237-266. doi: 10.1016/bs.acr.2021.07.006. Epub 2021 Aug 13.

Abstract

RAS proteins represent critical drivers of tumor development and thus are the focus of intense efforts to pharmacologically inhibit these proteins in human cancer. Although recent success has been attained in developing clinically efficacious inhibitors to KRAS, there remains a critical need for developing approaches to inhibit additional mutant RAS proteins. A number of anti-RAS biologics have been developed which reveal novel and potentially therapeutically targetable vulnerabilities in oncogenic RAS. This review will discuss the growing field of anti-RAS biologics and potential development of these reagents into new anti-RAS therapies.

摘要

RAS蛋白是肿瘤发展的关键驱动因素,因此是在人类癌症中通过药理学方法抑制这些蛋白的大量研究工作的重点。尽管最近在开发对KRAS具有临床疗效的抑制剂方面取得了成功,但仍迫切需要开发抑制其他突变RAS蛋白的方法。已经开发出多种抗RAS生物制剂,这些制剂揭示了致癌RAS中新型的、具有潜在治疗靶向性的弱点。本综述将讨论抗RAS生物制剂这一不断发展的领域,以及将这些试剂开发成新的抗RAS疗法的潜力。

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N Engl J Med. 2021 Jun 24;384(25):2371-2381. doi: 10.1056/NEJMoa2103695. Epub 2021 Jun 4.
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