Cell Type-Specific Roles of STAT3 Signaling in the Pathogenesis and Progression of K-ras Mutant Lung Adenocarcinoma.
Cell Type-Specific Roles of STAT3 Signaling in the Pathogenesis and Progression of K-ras Mutant Lung Adenocarcinoma.
复制标题
DOI：
10.3390/cancers14071785
复制
发表时间：
2022-03-31
期刊：
影响因子：
5.2
通讯作者：
Moghaddam SJ
中科院分区：
文献类型：
--
作者：
Clowers MJ;Moghaddam SJ
K-ras 基因突变的肺腺癌很难进行药理学靶向治疗，且致死率很高。因此，需要确定影响 K-ras 肿瘤发生的其他治疗靶点。其中一个竞争者是 STAT3，它是一种与 K-ras 突变相关的转录因子，通过肿瘤细胞内在和外在机制帮助肿瘤发生和进展。在这篇综述中，我们总结了表达 STAT3 的肺上皮和浸润免疫细胞、STAT3 在 K-ras 突变型肺腺癌中的作用，以及可能能够靶向 STAT3 的疗法。在世界范围内，肺癌，特别是K-ras突变型肺腺癌（KM-LUAD），因其发病率高、治愈率低而成为癌症死亡的主要原因。为了治疗和预防 KM-LUAD，迫切需要针对 K-ras 下游效应器和/或其协作途径的替代策略。促肿瘤炎症是癌症的一个标志，它强烈参与 KM-LUAD 的发生和进展。然而，我们对介导 K-ras 诱导的肺肿瘤发生的动态炎症机制、免疫调节途径和细胞特异性分子信号的了解严重不足。然而，在这种信号复杂性中，炎症通路正在成为可药物靶标：信号转导器和转录激活剂 3 (STAT3)。在这里，我们回顾了 STAT3 在 KM-LUAD 发病机制和进展中的细胞类型特异性功能，它可以作为针对这种难治性肺癌的个性化预防和治疗干预的新靶点。
Lung adenocarcinomas with mutations in the K-ras gene are hard to target pharmacologically and highly lethal. As a result, there is a need to identify other therapeutic targets that influence K-ras oncogenesis. One contender is STAT3, a transcription factor that is associated with K-ras mutations and aids tumor development and progression through tumor cell intrinsic and extrinsic mechanisms. In this review, we summarize the lung epithelial and infiltrating immune cells that express STAT3, the roles of STAT3 in K-ras mutant lung adenocarcinoma, and therapies that may be able to target STAT3. Worldwide, lung cancer, particularly K-ras mutant lung adenocarcinoma (KM-LUAD), is the leading cause of cancer mortality because of its high incidence and low cure rate. To treat and prevent KM-LUAD, there is an urgent unmet need for alternative strategies targeting downstream effectors of K-ras and/or its cooperating pathways. Tumor-promoting inflammation, an enabling hallmark of cancer, strongly participates in the development and progression of KM-LUAD. However, our knowledge of the dynamic inflammatory mechanisms, immunomodulatory pathways, and cell-specific molecular signals mediating K-ras-induced lung tumorigenesis is substantially deficient. Nevertheless, within this signaling complexity, an inflammatory pathway is emerging as a druggable target: signal transducer and activator of transcription 3 (STAT3). Here, we review the cell type-specific functions of STAT3 in the pathogenesis and progression of KM-LUAD that could serve as a new target for personalized preventive and therapeutic intervention for this intractable form of lung cancer.
登录
查看更多内容
DOI：
10.4049/jimmunol.1502043
发表时间：
2016-06-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Ding C;Chen X;Dascani P;Hu X;Bolli R;Zhang HG;Mcleish KR;Yan J
通讯作者：
Yan J
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
影响因子：
32.4
作者：
Chalmin, Fanny;Mignot, Gregoire;Ghiringhelli, Francois
通讯作者：
Ghiringhelli, Francois
影响因子：
11.2
作者：
Acuff, HB;Carter, KJ;Matrisian, LM
通讯作者：
Matrisian, LM
影响因子：
50.5
作者：
Barrera, L.;Montes-Servin, E.;Arrieta, O.
通讯作者：
Arrieta, O.