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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Conclusion As a critical regulator of inflammation and cell survival, the NFκB pathway is a promising target for diagnosing and treating kidney diseases. For modulation of the NFκB pathway in the clinic, a number of molecules can effectively inhibit NFκB signaling by targeting the receptors, associated adaptors, IKKs, IκBs and transcriptional regulators (144). There is further clinical evidence on small-molecule inhibitors of IKKα and NIK from recent trials on anti-cancer therapies (145). These clinical trials showed that the cancer-selective pharmacodynamic response of DTP3, the co-inhibitor...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
This study showed that potential vicious cycles underlying ARDs are quite diverse and unique, triggered by diverse and unique factors that do not usually progress with age, thus casting doubts on the possibility of discovering the single molecular cause of aging and developing the single anti-aging pill. Rather, each disease appears to require an individual approach. However, it still cannot be excluded that some or all of these cycles are triggered by fundamental processes of aging, such as chronic inflammation or accumulation of senescent cells. Nevertheless, experimental data showing clear cause and effect relationships...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Publication date: Available online 20 September 2018Source: CellAuthor(s): Larissa D. Cunha, Mao Yang, Robert Carter, Clifford Guy, Lacie Harris, Jeremy C. Crawford, Giovanni Quarato, Emilio Boada-Romero, Halime Kalkavan, Michael D.L. Johnson, Sivaraman Natarajan, Meghan E. Turnis, David Finkelstein, Joseph T. Opferman, Charles Gawad, Douglas R. GreenSummaryTargeting autophagy in cancer cells and in the tumor microenvironment are current goals of cancer therapy. However, components of canonical autophagy play roles in other biological processes, adding complexity to this goal. One such alternative function of autophagy pro...
Source: Cell - Category: Cytology Source Type: research
ONCOLOGY recently interviewed Dr. Eileen Parkes, whose laboratory studies the STING pathway, to find out why researchers are excited about targeting this pathway as a potential cancer therapy.
Source: CancerNetwork - Category: Cancer & Oncology Authors: Source Type: news
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
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