Targeting the interplay of cGAS-STING and ferroptosis by nanomedicine in the treatment of cancer.

IF 12.8 1区 医学 Q1 ONCOLOGY
Chunfei Li, Wenyan Zhao, Donghua Geng, Yuzi Jin, Wenzheng Guan
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Abstract

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway senses cytosolic DNA and triggers innate immune responses. Pharmacological activation of the cGAS-STING pathway by cGAS-STING agonists to overcome cancer drug resistance offers substantial potential to promote antitumor immunity. However, small-molecule STING agonists show rapid excretion, low bioavailability, non-specificity, and adverse effects, which limit their therapeutic efficacy and in vivo applications. The recent emergence of nanomedicine has profoundly revolutionized STING agonist delivery, promoting tumor-targeted delivery and offering new opportunities for tumor-specific immunotherapy. A growing body of evidence has shown that cGAS-STING interacts with ferroptosis in cancer cells. Targeting the interplay between cGAS-STING and ferroptosis using nanomedicines offers a novel cancer treatment regimen. In this review, we outline the principal components of the cGAS-STING signaling cascade and discuss its role in cancer biology. We also review the role of the interplay between cGAS-STING and ferroptosis in cancer genesis. We then focus on providing an overview of the latest findings and emerging concepts that leverage the interplay between cGAS-STING and ferroptosis by nanomedicine to kill cancers. Finally, we discuss the key limitations of the current therapeutic paradigm and possible strategies to overcome them. This article highlights some promising therapeutic avenues that leverage the interplay of cGAS-STING and ferroptosis by nanomedicine, which could be used to treat cancer.

利用纳米药物靶向cGAS-STING与铁下垂的相互作用治疗癌症。
环GMP-AMP合成酶(cGAS)-干扰素基因刺激因子(STING)通路感知胞质DNA并触发先天免疫反应。cGAS-STING激动剂通过药理激活cGAS-STING途径克服癌症耐药,为促进抗肿瘤免疫提供了巨大的潜力。然而,小分子STING激动剂具有排泄速度快、生物利用度低、非特异性和不良反应等特点,限制了其治疗效果和体内应用。近年来,纳米医学的出现深刻地改变了STING激动剂的递送,促进了肿瘤靶向递送,并为肿瘤特异性免疫治疗提供了新的机会。越来越多的证据表明,cGAS-STING与癌细胞中的铁下垂相互作用。利用纳米药物靶向cGAS-STING与铁下垂之间的相互作用,提供了一种新的癌症治疗方案。在这篇综述中,我们概述了cGAS-STING信号级联的主要成分,并讨论了其在癌症生物学中的作用。我们也回顾了cGAS-STING和铁下垂之间的相互作用在癌症发生中的作用。然后,我们重点介绍了利用纳米药物杀死癌症的cGAS-STING和铁下垂之间的相互作用的最新发现和新兴概念。最后,我们讨论了当前治疗范式的主要局限性和克服它们的可能策略。本文重点介绍了利用纳米药物利用cGAS-STING和铁下垂的相互作用的一些有前途的治疗途径,这些途径可用于治疗癌症。
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来源期刊
CiteScore
18.20
自引率
1.80%
发文量
333
审稿时长
1 months
期刊介绍: The Journal of Experimental & Clinical Cancer Research is an esteemed peer-reviewed publication that focuses on cancer research, encompassing everything from fundamental discoveries to practical applications. We welcome submissions that showcase groundbreaking advancements in the field of cancer research, especially those that bridge the gap between laboratory findings and clinical implementation. Our goal is to foster a deeper understanding of cancer, improve prevention and detection strategies, facilitate accurate diagnosis, and enhance treatment options. We are particularly interested in manuscripts that shed light on the mechanisms behind the development and progression of cancer, including metastasis. Additionally, we encourage submissions that explore molecular alterations or biomarkers that can help predict the efficacy of different treatments or identify drug resistance. Translational research related to targeted therapies, personalized medicine, tumor immunotherapy, and innovative approaches applicable to clinical investigations are also of great interest to us. We provide a platform for the dissemination of large-scale molecular characterizations of human tumors and encourage researchers to share their insights, discoveries, and methodologies with the wider scientific community. By publishing high-quality research articles, reviews, and commentaries, the Journal of Experimental & Clinical Cancer Research strives to contribute to the continuous improvement of cancer care and make a meaningful impact on patients' lives.
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