Covalent inhibitor targets KRasG12C: A new paradigm for drugging the undruggable and challenges ahead
文献类型：期刊论文
| 作者 | Li, Hui-yu1,2; Qi, Wei-liang1,2,3; Wang, Yu-xiang2; Meng, Ling-hua1,2,4
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| 刊名 | GENES & DISEASES
 |
| 出版日期 | 2023-03-01 |
| 卷号 | 10期号:2页码:403-414 |
| 关键词 | Biomarkers Covalent KRasG12Cinhibitors Drug resistance Human cancers KRASG12Cmutation |
| ISSN号 | 2352-4820 |
| DOI | 10.1016/j.gendis.2021.08.011 |
| 通讯作者 | Wang, Yu-xiang(yxwang@simm.ac.cn) ; Meng, Ling-hua(lhmeng@simm.ac.cn) |
| 英文摘要 | KRAS is one of the most commonly mutated oncogenes in cancers and therapeutics directly targeting the KRas have been challenging. Among the different known mutants, KRasG12C has been proved to be successfully targeted recently. Several covalent inhibitors selectively targeting KRasG12C have shown promising efficacy against cancers harboring KRASG12C mutation in clinical trials and AMG510 (sotorasib) has been approved for the treat-ment of KRASG12C-mutated locally advanced or metastatic non-small cell lung cancer. Howev-er, the overall responsive rate of KRasG12C inhibitors was around 50% in patients with non-small cell lung cancer and the efficacy in patients with colorectal cancer or appendiceal cancer ap-pears to be less desirable. It is of great importance to discover biomarkers to distinguish pa-tients who are likely benefitted. Moreover, adaptive resistance would occur inevitably with the persistent administration like other molecularly targeted therapies. Several combinatorial regimens have been studied in an effort to potentiate the efficacy of KRasG12C inhibitors in pre -clinical settings. This review summarized the recent progress of covalent KRasG12C inhibitors with a focus on identifying biomarkers to predict or monitor the efficacy and proposing rational drug combinations based on elucidation of the mechanisms of drug resistance. (c) 2021 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons. org/licenses/by-nc-nd/4.0/). |
| WOS关键词 | K-RAS ; AMG 510 ; KRAS(G12C) INHIBITION ; KRYSTAL-1 ACTIVITY ; ADAGRASIB MRTX849 ; MUTANT KRAS ; CANCER ; G12C ; DISCOVERY ; ONCOGENES |
| 资助项目 | National Natural Science Foundation of China[81773760] ; National Natural Science Foundation of China[81973345] ; National Natural Science Foundation of China[82104199] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Genetics & Heredity |
| 语种 | 英语 |
| WOS记录号 | WOS:000994784500001 |
| 出版者 | KEAI PUBLISHING LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/306647]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Wang, Yu-xiang; Meng, Ling-hua |
| 作者单位 | 1.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, Shanghai 201203, Peoples R China 3.Nanchang Univ, Coll Pharm, Nanchang 330006, Jiangxi, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, 501 Haike Rd, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Li, Hui-yu,Qi, Wei-liang,Wang, Yu-xiang,et al. Covalent inhibitor targets KRasG12C: A new paradigm for drugging the undruggable and challenges ahead[J]. GENES & DISEASES,2023,10(2):403-414. |
| APA | Li, Hui-yu,Qi, Wei-liang,Wang, Yu-xiang,&Meng, Ling-hua.(2023).Covalent inhibitor targets KRasG12C: A new paradigm for drugging the undruggable and challenges ahead.GENES & DISEASES,10(2),403-414. |
| MLA | Li, Hui-yu,et al."Covalent inhibitor targets KRasG12C: A new paradigm for drugging the undruggable and challenges ahead".GENES & DISEASES 10.2(2023):403-414. |
入库方式： OAI收割
来源：上海药物研究所
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