Pharmacological STING Activation Is a Potential Alternative to Overcome Drug-Resistance in Melanoma

Chipurupalli, Sandhya; Ganesan, Raja; Dhanabal, S P; Kumar, M N Satish; Robinson, Nirmal

doi:10.3389/fonc.2020.00758

Cited by 24 publications

(28 citation statements)

References 32 publications

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“…However, the use of the STING agonist DMXAA combined with caspase inhibition in vivo increases TNF and IFN levels subsequently leading to necroptosis, but this resulted in increased mortality due to septic shock [74]. Although, DMXAA is a failure in clinics due to its inability to effectively activate human STING, small molecule STING agonist amidobenzimidazole (ABZI) has been reported to bind and activate both human and mouse STING [80,81]. Therefore, such STING agonists in clinical trials will need to be assessed for their roles in triggering necroptosis without extensive secondary effects.…”

Section: Interplay Between the Cgas-sting Signaling And Necroptosismentioning

confidence: 99%

Crosstalk between cGAS–STING signaling and cell death

2020

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Cytosolic nucleic acid sensors have a critical role in detecting endogenous nucleic acids to initiate innate immune responses during microbial infections and/or cell death. Several seminal studies over the past decade have delineated the conserved mechanism of cytosolic DNA sensor cyclic GMP-AMP synthase (cGAS) and the downstream signaling adapter stimulator of interferon genes (STING) in mediating innate immune signaling pathways as a host defense mechanism. Besides the predominant role in microbial infections and inflammatory diseases, there is an increased attention on alternative functional responses of cGAS-STING-mediated signaling. Here we review the complexity of interactions between the cGAS-STING signaling and cell death pathways. A better understanding of molecular mechanisms of this interplay is important with regard to the development of new therapeutics targeting cGAS-STING signaling in cancer, infectious, and chronic inflammatory diseases. Facts • Cytosolic DNA stimulates various signaling pathways that often lead to different modes of cell death. • The cGAS-STING pathway recognizes cytosolic DNA to initiate type I interferon production. • Autophagy has a dual role in cGAS-STING signaling, by initiating inflammatory responses and by targeting STING for degradation.

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Section: Interplay Between the Cgas-sting Signaling And Necroptosismentioning

confidence: 99%

Crosstalk between cGAS–STING signaling and cell death

2020

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“…Manganese potentiates the anti-tumor immune response as a STING agonist [ 107 ]. Dimeric aminobenzimidazole (diABZI) is another STING agonist that promotes tumor cell death in melanoma in combination with BRAF inhibitors [ 108 ]. Cytomegalovirus (CMV) acts as a STING agonist in tumors.…”

Section: Sting Strategy For Skin Cancersmentioning

confidence: 99%

STING Signaling and Skin Cancers

Sato

Sawada

Nakamura

2021

Cancers

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Recent developments in immunotherapy against malignancies overcome the disadvantages of traditional systemic treatments; however, this immune checkpoint treatment is not perfect and cannot obtain a satisfactory clinical outcome in all cases. Therefore, an additional therapeutic option for malignancy is needed in oncology. Stimulator of interferon genes (STING) has recently been highlighted as a strong type I interferon driver and shows anti-tumor immunity against various malignancies. STING-targeted anti-tumor immunotherapy is expected to enhance the anti-tumor effects and clinical outcomes of immunotherapy against malignancies. In this review, we focus on recent advancements in the knowledge gained from research on STING signaling in skin cancers. In addition to the limitations of STING-targeted immunotherapy, we also discuss the clinical application of STING agonists in the treatment of skin cancer.

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“…Separate groups of researchers have reached an agreement that direct activation of STING can robustly block SARS-CoV-2 infection. Moreover, they found that the STING agonist, diABZI and diABZI-4, can effectively restrict SARS-CoV-2 replication ( Chipurupalli et al, 2020 ; Zhu et al, 2021 ). Furthermore, Wu et al (2021) expanded the function of a novel STING agonist, CDG SF , as an adjuvant for the SARS-CoV-2 vaccine.…”

Section: Severe Acute Respiratory Syndrome Coronavirus-2 Infection and Cyclic Gmp-amp Synthase-stimulator Of Interferon Genesmentioning

confidence: 99%

The Regulatory Network of Cyclic GMP-AMP Synthase-Stimulator of Interferon Genes Pathway in Viral Evasion

et al. 2021

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Virus infection has been consistently threatening public health. The cyclic GMP-AMP synthase (cGAS)-Stimulator of Interferon Genes (STING) pathway is a critical defender to sense various pathogens and trigger innate immunity of mammalian cells. cGAS recognizes the pathogenic DNA in the cytosol and then synthesizes 2′3′-cyclic GMP-AMP (2′3′cGAMP). As the second messenger, cGAMP activates STING and induces the following cascade to produce type I interferon (IFN-I) to protect against infections. However, viruses have evolved numerous strategies to hinder the cGAS-STING signal transduction, promoting their immune evasion. Here we outline the current status of the viral evasion mechanism underlying the regulation of the cGAS-STING pathway, focusing on how post-transcriptional modifications, viral proteins, and non-coding RNAs involve innate immunity during viral infection, attempting to inspire new targets discovery and uncover potential clinical antiviral treatments.

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Pharmacological STING Activation Is a Potential Alternative to Overcome Drug-Resistance in Melanoma

Cited by 24 publications

References 32 publications

Crosstalk between cGAS–STING signaling and cell death

Crosstalk between cGAS–STING signaling and cell death

STING Signaling and Skin Cancers

The Regulatory Network of Cyclic GMP-AMP Synthase-Stimulator of Interferon Genes Pathway in Viral Evasion

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