Buzz Continues Over STING Inhibitors

STING (stimulator of interferon genes) inhibitors have been shown to help T cells thrive and work synergistically with other cancer therapies, so new trials are underway to test whether they can be used to improve response in certain patients.
Source: CancerNetwork - Category: Cancer & Oncology Authors: Tags: Immuno Oncology News Source Type: news

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Abstract Stimulator of IFN genes (STING) is essential for the DNA-sensing innate immune pathway. Recently, evidence is emerging that suggests STING also plays important roles in autoimmunity, cancer therapy, and senescence. Although a multitude of post-translational modifications that regulate the STING pathway have been discovered, the cellular events that guide STING translocation remain unclear. Here, we show, paradoxically, that both BAPTA-AM-mediated calcium depletion and ionomycin-induced calcium elevation suppress STING translocation and STING-mediated IFN-β production. We demonstrate that the mitochon...
Source: Biochemical and Biophysical Research communications - Category: Biochemistry Authors: Tags: Biochem Biophys Res Commun Source Type: research
Publication date: 12 December 2017 Source:Cell Reports, Volume 21, Issue 11 Author(s): Vijay K. Gonugunta, Tomomi Sakai, Vladislav Pokatayev, Kun Yang, Jianjun Wu, Nicole Dobbs, Nan Yan STING is an endoplasmic reticulum (ER)-associated transmembrane protein that turns on and quickly turns off downstream signaling as it translocates from the ER to vesicles. How STING signaling is attenuated during trafficking remains poorly understood. Here, we show that trafficking-mediated STING degradation requires ER exit and function of vacuolar ATPase complex. Late-stage STING vesicles are sorted to Rab7-positive endolysosomes for de...
Source: Cell Reports - Category: Cytology Source Type: research
Conclusion It is highly relevant to deepen the study of the nucleic acid-sensing mechanisms to develop new pharmacological approaches to engage these pathways within the tumour microenvironment. Indeed, further clarification will be functional to develop advanced anticancer strategies or to design new vaccines formulation. PMID: 29086701 [PubMed - as supplied by publisher]
Source: Recent Patents on Anti-Cancer Drug Discovery - Category: Cancer & Oncology Tags: Recent Pat Anticancer Drug Discov Source Type: research
Nature advance online publication 31 July 2017. doi:10.1038/nature23470 Authors: Shane M. Harding, Joseph L. Benci, Jerome Irianto, Dennis E. Discher, Andy J. Minn &Roger A. Greenberg Inflammatory gene expression following genotoxic cancer therapy is well documented, yet the events underlying its induction remain poorly understood. Inflammatory cytokines modify the tumour microenvironment by recruiting immune cells and are critical for both local and systemic (abscopal) tumour responses to radiotherapy. A poorly understood feature of these responses is the delayed onset (days), in contrast to the acute DNA-damage resp...
Source: Nature AOP - Category: Research Authors: Tags: Letter Source Type: research
Stimulator of interferon genes (STING) is a DNA sensor and an important cytoplasmic adaptor for other DNA sensors, such as Z-DNA binding protein 1 (DAI), DEAD-box helicase 41 (DDX41), and interferon- γ-inducible protein 16 (IFI16). The activation of STING signaling leads to the production of type I interferons and some other pro-inflammatory cytokines, and is critical for host defense against viral infection. Recent accumulating evidences suggest that STING is also involved in tumor development . However, the role of STING signaling in tumorigenesis is complicated, and a comprehensive review is still lacking.
Source: Cancer Letters - Category: Cancer & Oncology Authors: Source Type: research
In this study we demonstrate the use of clustered regularly interspaced short palindromic repeats (CRISPR)-based epigenome editing to alter cell response to inflammatory environments by repressing inflammatory cytokine cell receptors, specifically TNFR1 and IL1R1. This has applications for many inflammatory-driven diseases. It could be applied for arthritis or to therapeutic cells that are being delivered to inflammatory environments that need to be protected from inflammation." In chronic back pain, for example, slipped or herniated discs are a result of damaged tissue when inflammation causes cells to create ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
The most important projects in cancer research are those that might produce therapies effective against many different types of cancer. There are too many varieties of cancer and individual tumors can evolve too rapidly for the research community to achieve its goals by working on highly specific therapies. To defeat cancer within the next few decades, the aim must be to produce broadly effective therapies, targeting common mechanisms and vulnerabilities shared by many or all cancers. There projects cost the same as more narrowly applicable approaches, but are much more cost-effective for the results they might produce. Th...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs
A major subset of human cancers shows evidence for spontaneous adaptive immunity, which is reflected by the presence of infiltrating CD8+ T cells specific for tumor antigens within the tumor microenvironment. This observation has raised the question of which innate immune sensing pathway might detect the presence of cancer and lead to a natural adaptive antitumor immune response in the absence of exogenous infectious pathogens. Evidence for a critical functional role for type I IFNs led to interrogation of candidate innate immune sensing pathways that might be triggered by tumor presence and induce type I IFN production. S...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
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Source: International Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Research Article Source Type: research
The stromal cells of the tumor microenvironment play a critical role in tumor progression, and are therefore attractive targets for cancer therapy. We previously used the stromal targeting agent, 5,6-dimethylxanthenone-4-acetic acid (DMXAA), to demonstrate how tumor and stromal interactions can be manipulated to favor anti-tumor activity against human melanoma xenografts in immunodeficient mice, mediated by neutrophils and macrophages. An ideal stromal targeting agent would be effective against established metastases as well as primary tumors. In order to design such therapies, and to assess their potential, a better under...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Innate Immune Cells in the Tumor Microenvironment Source Type: research
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