Narrative review of emerging roles for AKT-mTOR signaling in cancer radioimmunotherapy.
Narrative review of emerging roles for AKT-mTOR signaling in cancer radioimmunotherapy.
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DOI：
10.21037/atm-21-4544
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发表时间：
2021-10
影响因子：
--
通讯作者：
He Z
中科院分区：
文献类型：
--
作者：
Shen C;He Y;Chen Q;Feng H;Williams TM;Lu Y;He Z
总结AKT-mTOR信号通路在肿瘤细胞DNA损伤反应和PD-L1表达调控中的作用，提出肿瘤免疫治疗时代靶向AKT-mTOR信号通路联合放射免疫治疗的新策略。免疫治疗极大地改善了许多癌症患者的临床疗效，改变了癌症患者治疗的格局。然而，只有一小部分癌症患者（约20-30%）受益于基于免疫检查点阻断的免疫治疗。目前的挑战是找到生物标志物来预测患者对免疫治疗的反应，以及使患者对免疫治疗敏感的策略。以mTOR、AKT、耐药、DNA损伤反应、免疫治疗、PD-L1、DNA修复、放射免疫治疗为关键词检索PUBMED 2000-2021年发表的相关文献。超过50%的癌症患者在治疗过程中接受放射治疗。放疗已被证明通过影响全身免疫来减少局部辐照肿瘤的生长以及转移性非辐照肿瘤（体外效应）。一致地，免疫疗法已被证明可以增强放射治疗，超过一百项针对癌症类型的放射与免疫疗法（放射免疫疗法）相结合的临床试验。然而，目前可用的数据显示，放射免疫疗法的试验效果有限。AKT-mTOR信号是一种主要的肿瘤生长促进途径，在大多数癌症中表达上调。AKT-mTOR信号被生长因子以及包括放射治疗在内的基因毒性应激激活。重要的是，最近的进展表明，AKT-mTOR是癌症中调节DNA损伤修复和PD-L1水平的主要信号通路之一。这些最新进展清楚地表明，靶向AKT-mTOR信号与放射免疫治疗相结合是一种新的癌症治疗策略。
To summarize the roles of AKT-mTOR signaling in the regulation of the DNA damage response and PD-L1 expression in cancer cells, and propose a novel strategy of targeting AKT-mTOR signaling in combination with radioimmunotherapy in the era of cancer immunotherapy Immunotherapy has greatly improved the clinical outcomes of many cancer patients and has changed the landscape of cancer patient management. However, only a small subgroup of cancer patients (~20–30%) benefit from immune checkpoint blockade-based immunotherapy. The current challenge is to find biomarkers to predict the response of patients to immunotherapy and strategies to sensitize patients to immunotherapy. Search and review the literature which were published in PUBMED from 2000–2021 with the key words mTOR, AKT, drug resistance, DNA damage response, immunotherapy, PD-L1, DNA repair, radioimmunotherapy. More than 50% of cancer patients receive radiotherapy during their course of treatment. Radiotherapy has been shown to reduce the growth of locally irradiated tumors as well as metastatic non-irradiated tumors (abscopal effects) by affecting systemic immunity. Consistently, immunotherapy has been demonstrated to enhance radiotherapy with more than one hundred clinical trials of radiation in combination with immunotherapy (radioimmunotherapy) across cancer types. Nevertheless, current available data have shown limited efficacy of trials testing radioimmunotherapy. AKT-mTOR signaling is a major tumor growth-promoting pathway and is upregulated in most cancers. AKT-mTOR signaling is activated by growth factors as well as genotoxic stresses including radiotherapy. Importantly, recent advances have shown that AKT-mTOR is one of the main signaling pathways that regulate DNA damage repair as well as PD-L1 levels in cancers. These recent advances clearly suggest a novel cancer therapy strategy by targeting AKT-mTOR signaling in combination with radioimmunotherapy.
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DOI：
10.1126/science.aac9935
发表时间：
2016-04-08
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Casey SC;Tong L;Li Y;Do R;Walz S;Fitzgerald KN;Gouw AM;Baylot V;Gütgemann I;Eilers M;Felsher DW
通讯作者：
Felsher DW
影响因子：
8
作者：
Deng, Liang;Qian, Guoqing;Sun, Shi-Yong
通讯作者：
Sun, Shi-Yong
影响因子：
64.8
作者：
Cunningham, John T.;Rodgers, Joseph T.;Puigserver, Pere
通讯作者：
Puigserver, Pere
影响因子：
3.7
作者：
Ethier, Chantal;Tardif, Maxime;Poirier, Guy G.
通讯作者：
Poirier, Guy G.
影响因子：
5.3
作者：
Fingar, DC;Richardson, CJ;Blenis, J
通讯作者：
Blenis, J