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Targeting the sphingosine-1-phosphate axis in cancer, inflammation and beyond

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TLDR
The ways in which S1P might be therapeutically targeted are discussed — for example, via the development of chemical inhibitors that target the generation, transport and degradation of S 1P and via thedevelopment of specific S1p receptor agonists.
Abstract
The bioactive lipid sphingosine-1-phosphate (S1P) is involved in multiple cellular signalling systems and has a pivotal role in the control of immune cell trafficking. As such, S1P has been implicated in disorders such as cancer and inflammatory diseases. This Review discusses the ways in which S1P might be therapeutically targeted — for example, via the development of chemical inhibitors that target the generation, transport and degradation of S1P and via the development of specific S1P receptor agonists. We also highlight recent conflicting results observed in preclinical studies targeting S1P and discuss ongoing clinical trials in this field.

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Journal ArticleDOI

Mechanisms of sphingosine 1-phosphate receptor signalling in cancer.

TL;DR: There is strong evidence implicating the involvement of S1P receptors (S1PRs) in cancer progression and the recent evidence to suggest cross-talk between the S1 PRs and other cellular signalling pathways in cancer.
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Resistance of Cancer Cells to Targeted Therapies Through the Activation of Compensating Signaling Loops

TL;DR: The treatment of HNSCC with a specific inhibitor of c-Src initially resulted in reduced Stat3 and Stat5 activation and subsequently an arrest of cell proliferation and increased apoptosis, indicating that the inhibition of a single tyrosine kinase might not be sufficient to induce lasting therapeutic effects in cancer patients.
Journal ArticleDOI

Non-coding RNAs: the new central dogma of cancer biology.

TL;DR: A comprehensive review of the various ncRNAs and their functional roles in cancer, and the pre-clinical and clinical development of ncRNA-based therapeutics is provided.
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Sphingosine 1-phosphate Receptor Modulator Therapy for Multiple Sclerosis: Differential Downstream Receptor Signalling and Clinical Profile Effects

TL;DR: The S1P pathway, the characteristics and S1PR binding profiles of S1 PR modulators, the mechanisms of action of S2PR modulators with regard to immune cell trafficking and neuroprotection in MS are reviewed, together with a summary of the clinical effectiveness of the S1pr modulators that are approved or in late-stage development for patients with MS.
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Targeting the Hippo Signaling Pathway for Tissue Regeneration and Cancer Therapy

TL;DR: The Hippo signaling pathway is a highly-conserved developmental pathway that plays an essential role in organ size control, tumor suppression, tissue regeneration and stem cell self-renewal, and the role of the Hippo pathway in tissue repair and cancer is presented.
References
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Journal ArticleDOI

STATs in cancer inflammation and immunity: a leading role for STAT3

TL;DR: Signal transducer and activator of transcription proteins are central in determining whether immune responses in the tumour microenvironment promote or inhibit cancer, and STAT3 is a promising target to redirect inflammation for cancer therapy.
Journal ArticleDOI

Principles of bioactive lipid signalling: lessons from sphingolipids

TL;DR: An understanding of the complex pathways of sphingolipid metabolism and the mechanisms that regulate lipid generation and lipid action is required to understand the mechanisms of cell growth, death, senescence, adhesion, migration, inflammation, angiogenesis and intracellular trafficking.
Journal ArticleDOI

The many roles of histone deacetylases in development and physiology: Implications for disease and therapy

TL;DR: In this article, the expression of many HDAC isoforms in eukaryotic cells raises questions about their possible specificity or redundancy, and whether they control global or specific programs of gene expression.
Journal Article

Heart-lung transplantation.

TL;DR: A broad overview of the various grounds upon which this difference is likely based and discuss recent advances in each area: 1) criteria for the selection of candidates and donors, 2) methods for ex-vivo preservation of donor organs, 3) technical execution of the operative procedure, and 4) prevention of postoperative infection as discussed by the authors.
Journal ArticleDOI

Mixed Lineage Kinase Domain-like Protein Mediates Necrosis Signaling Downstream of RIP3 Kinase

TL;DR: The identification of a small molecule called necrosulfonamide that specifically blocks necrosis downstream of RIP3 activation is reported, which implicate MLKL as a key mediator of necrosis signaling downstream of the kinase RIP3.
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