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LKB1 与肿瘤代谢:肺癌中免疫和血管生成微环境的相互作用。

LKB1 and Tumor Metabolism: The Interplay of Immune and Angiogenic Microenvironment in Lung Cancer.

机构信息

Medical Oncology 2, Istituto Oncologico Veneto IOV- IRCCS, 35128 Padova, Italy.

Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto IOV- IRCCS, 35128 Padova, Italy.

出版信息

Int J Mol Sci. 2019 Apr 16;20(8):1874. doi: 10.3390/ijms20081874.

Abstract

Liver kinase B1 () is a tumor suppressor gene whose inactivation is frequent in different tumor types, especially in lung adenocarcinoma (about 30% of cases). LKB1 has an essential role in the control of cellular redox homeostasis by regulating ROS production and detoxification. Loss of LKB1 makes the tumor cell more sensitive to oxidative stress and consequently to stress-inducing treatments, such as chemotherapy and radiotherapy. LKB1 loss triggers complex changes in tumor microenvironment, supporting a role in the regulation of angiogenesis and suggesting a potential role in the response to anti-angiogenic treatment. On the other hand, LKB1 deficiency can promote an immunosuppressive microenvironment and may be involved in primary resistance to anti-PD-1/anti-PD-L1, as it has been reported in lung cancer. The aim of this review is to discuss interactions of LKB1 with the tumor microenvironment and the potential applications of this knowledge in predicting response to treatment in lung cancer.

摘要

肝激酶 B1(LKB1)是一种抑癌基因,其失活在不同类型的肿瘤中很常见,尤其是在肺腺癌(约 30%的病例中)。LKB1 通过调节 ROS 的产生和解毒在控制细胞氧化还原平衡方面发挥着重要作用。LKB1 的缺失使肿瘤细胞对氧化应激更敏感,因此更容易受到化疗和放疗等应激诱导治疗的影响。LKB1 的缺失触发肿瘤微环境的复杂变化,支持其在血管生成调节中的作用,并提示其在抗血管生成治疗反应中的潜在作用。另一方面,LKB1 缺乏可促进免疫抑制性微环境,并且可能与原发性抗 PD-1/抗 PD-L1 耐药有关,正如在肺癌中所报道的那样。本综述的目的是讨论 LKB1 与肿瘤微环境的相互作用,以及这些知识在预测肺癌治疗反应方面的潜在应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfcb/6514929/f8bb1a1e7df9/ijms-20-01874-g001.jpg

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