KRAS-Mutant Lung Cancer: Targeting Molecular and Immunologic Pathways, Therapeutic Advantages and Restrictions.
KRAS-Mutant Lung Cancer: Targeting Molecular and Immunologic Pathways, Therapeutic Advantages and Restrictions.
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KRAS突变肺癌：靶向分子和免疫途径、治疗优势和限制。
作者：
RAS突变是人类癌症中最常见的致癌突变之一。在RAS突变中，KRAS的频率最高，几乎30%的非小细胞肺癌（NSCLC）患者中存在KRAS。肺癌是癌症中死亡率最高的原因，因为它具有极强的侵袭性和较晚的诊断。高死亡率是众多调查和临床试验的原因，以发现针对KRAS的适当治疗药物。这些方法包括：直接针对KRAS；合成致命性伴侣抑制剂；靶向KRAS膜缔合及其代谢重布线自噬抑制剂;下游抑制剂;免疫疗法和其他免疫模式，如调节炎症信号转录因子（如STAT3）。不幸的是，由于多种限制性机制（包括共突变的存在），其中大多数都遇到了有限的治疗效果。在这篇综述中，我们计划总结过去和最近正在研究的治疗方法，以及它们的治疗成功率和潜在的限制。这将为改进治疗这种致命疾病的新药的设计提供有用的信息。
RAS mutations are among the most common oncogenic mutations in human cancers. Among RAS mutations, KRAS has the highest frequency and is present in almost 30% of non-small-cell lung cancer (NSCLC) patients. Lung cancer is the number one cause of mortality among cancers as a consequence of outrageous aggressiveness and late diagnosis. High mortality rates have been the reason behind numerous investigations and clinical trials to discover proper therapeutic agents targeting KRAS. These approaches include the following: direct KRAS targeting; synthetic lethality partner inhibitors; targeting of KRAS membrane association and associated metabolic rewiring; autophagy inhibitors; downstream inhibitors; and immunotherapies and other immune-modalities such as modulating inflammatory signaling transcription factors (e.g., STAT3). The majority of these have unfortunately encountered limited therapeutic outcomes due to multiple restrictive mechanisms including the presence of co-mutations. In this review we plan to summarize the past and most recent therapies under investigation, along with their therapeutic success rate and potential restrictions. This will provide useful information to improve the design of novel agents for treatment of this deadly disease.
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影响因子：
6
作者：
Armon S;Hofman P;Ilié M
通讯作者：
Ilié M
同时发生的基因组改变对KRAS突变非小细胞肺癌患者结局的影响。
DOI：
10.1158/1078-0432.ccr-17-1841
发表时间：
2018-01-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Arbour KC;Jordan E;Kim HR;Dienstag J;Yu HA;Sanchez-Vega F;Lito P;Berger M;Solit DB;Hellmann M;Kris MG;Rudin CM;Ni A;Arcila M;Ladanyi M;Riely GJ
通讯作者：
Riely GJ
影响因子：
2.9
作者：
Chen L;Chen F;Li J;Pu Y;Yang C;Wang Y;Lei Y;Huang Y
通讯作者：
Huang Y
影响因子：
16.6
作者：
Caetano MS;Hassane M;Van HT;Bugarin E;Cumpian AM;McDowell CL;Cavazos CG;Zhang H;Deng S;Diao L;Wang J;Evans SE;Behrens C;Wistuba II;Fuqua SAW;Lin H;Stabile LP;Watowich SS;Kadara H;Moghaddam SJ
通讯作者：
Moghaddam SJ
DOI：
10.1038/nrm3255
发表时间：
2011-12-22
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
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