Emerging strategies to target RAS signaling in human cancer therapy.
Emerging strategies to target RAS signaling in human cancer therapy.
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人类癌症治疗中针对 RAS 信号传导的新兴策略
DOI：
10.1186/s13045-021-01127-w
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发表时间：
2021-07-23
影响因子：
28.5
通讯作者：
Wang P
中科院分区：
文献类型：
--
作者：
Chen K;Zhang Y;Qian L;Wang P
RAS突变（HRAS、NRAS和KRAS）是最常见的致癌基因之一，约19%的癌症患者携带RAS突变。携带RAS突变的细胞倾向于发生恶性转化并表现出恶性表型。RAS的突变状态与患者的临床病理学特征相关，例如粘液型和低分化，以及某些类型的人类癌症对抗EGFR治疗的反应。尽管RAS蛋白曾被认为是RAS突变肿瘤的潜在靶点，但由于RAS蛋白抑制剂的连续失败，它曾被认为是不可治疗的靶点。然而，最近关于RAS的结构、信号传导和功能的研究为RAS靶向药物的开发提供了线索，特别是Lumakras（sotorasib，AMG 510）获批用于治疗KRASG12C突变型NSCLC患者。因此，在这里，我们全面审查RAS突变在人类癌症，特别是集中在新兴的战略，最近已经开发的RAS靶向治疗。
RAS mutations (HRAS, NRAS, and KRAS) are among the most common oncogenes, and around 19% of patients with cancer harbor RAS mutations. Cells harboring RAS mutations tend to undergo malignant transformation and exhibit malignant phenotypes. The mutational status of RAS correlates with the clinicopathological features of patients, such as mucinous type and poor differentiation, as well as response to anti-EGFR therapies in certain types of human cancers. Although RAS protein had been considered as a potential target for tumors with RAS mutations, it was once referred to as a undruggable target due to the consecutive failure in the discovery of RAS protein inhibitors. However, recent studies on the structure, signaling, and function of RAS have shed light on the development of RAS-targeting drugs, especially with the approval of Lumakras (sotorasib, AMG510) in treatment of KRASG12C-mutant NSCLC patients. Therefore, here we fully review RAS mutations in human cancer and especially focus on emerging strategies that have been recently developed for RAS-targeting therapy.
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影响因子：
51.1
作者：
Ascierto, Paolo A.;Schadendorf, Dirk;Dummer, Reinhard
通讯作者：
Dummer, Reinhard
DOI：
10.1056/nejmoa2105281
发表时间：
2021-06-24
期刊：
The New England journal of medicine
影响因子：
--
作者：
Awad MM;Liu S;Rybkin II;Arbour KC;Dilly J;Zhu VW;Johnson ML;Heist RS;Patil T;Riely GJ;Jacobson JO;Yang X;Persky NS;Root DE;Lowder KE;Feng H;Zhang SS;Haigis KM;Hung YP;Sholl LM;Wolpin BM;Wiese J;Christiansen J;Lee J;Schrock AB;Lim LP;Garg K;Li M;Engstrom LD;Waters L;Lawson JD;Olson P;Lito P;Ou SI;Christensen JG;Jänne PA;Aguirre AJ
通讯作者：
Aguirre AJ
影响因子：
64.8
作者：
Canon, Jude;Rex, Karen;Lipford, J. Russell
通讯作者：
Lipford, J. Russell
影响因子：
11.5
作者：
Bedard, Philippe L.;Tabernero, Josep;Sessa, Cristiana
通讯作者：
Sessa, Cristiana
影响因子：
45.3
作者：
Allegra, Carmen J.;Jessup, J. Milburn;Schilsky, Richard L.
通讯作者：
Schilsky, Richard L.