Targeting the“undruggable”cancer driver genes:Ras,myc,and tp53  

作　　者：XINGBO WU DAN PAN SHOUYI TANG YINGQIANG SHEN 

机构地区：[1]State Key Laboratory of Oral Diseases,National Clinical Research Center for Oral Diseases,Research Unit of Oral Carcinogenesis and Management,Chinese Academy of Medical Sciences,West China Hospital of Stomatology,Sichuan University,Chengdu,610041,China

出　　处：《BIOCELL》2023年第7期1459-1472,共14页生物细胞（英文）

基　　金：supported by Grants from the National Natural Science Foundation of China(81902784);the CAMS Innovation Fund for Medical Sciences(CIFMS,2019-I2M-5-004);the Fund of Sichuan Provincial Department of Science and Technology(2022YFSY0058);the Research Funding(RCDWJS 2020-20);the Research and Development Program(RD-02-202002)from West China School/Hospital of Stomatology Sichuan University.

摘　　要：The term“undruggable”is to describe molecules that are not targetable or at least hard to target pharmacologically.Unfortunately,some targets with potent oncogenic activity fall into this category,and currently little is known about how to solve this problem,which largely hampered drug research on human cancers.Ras,as one of the most common oncogenes,was previously considered“undruggable”,but in recent years,a few small molecules like Sotorasib(AMG-510)have emerged and proved their targeted anti-cancer effects.Further,myc,as one of the most studied oncogenes,and tp53,being the most common tumor suppressor genes,are both considered“undruggable”.Many attempts have been made to target these“undruggable”targets,but little progress has been made yet.This article summarizes the current progress of direct and indirect targeting approaches for ras,myc,two oncogenes,and tp53,a tumor suppressor gene.These are potential therapeutic targets but are considered“undruggable”.We conclude with some emerging research approaches like proteolysis targeting chimeras(PROTACs),cancer vaccines,and artificial intelligence(AI)-based drug discovery,which might provide new cues for cancer intervention.Therefore,this review sets out to clarify the current status of targeted anti-cancer drug research,and the insights gained from this review may be of assistance to learn from experience and find new ideas in developing new chemicals that directly target such“undruggable”molecules.

关 键 词：RAS MYC TP53 Antineoplastic agents PHARMACOLOGY Oncogene proteins Antagonists and inhibitors 

分 类 号：R730[医药卫生—肿瘤]