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Open AccessJournal ArticleDOI

The multifaceted role of chromosomal instability in cancer and its microenvironment

Samuel F. Bakhoum, +1 more
- 06 Sep 2018 - 
- Vol. 174, Iss: 6, pp 1347-1360
TLDR
These multipronged effects distinguish CIN as a central driver of tumor evolution and as a genomic source for the crosstalk between the tumor and its microenvironment, in the course of immune editing and evasion.
About
This article is published in Cell.The article was published on 2018-09-06 and is currently open access. It has received 355 citations till now. The article focuses on the topics: Chromosome instability & Tumor microenvironment.

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Citations
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Tumour evolution in hepatocellular carcinoma.

TL;DR: The molecular heterogeneity of hepatocellular carcinoma, the intrinsic and extrinsic factors that stimulate tumour evolution and how this information can be leveraged to improve the clinical management of patients with this disease are discussed.
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The Cytosolic DNA-Sensing cGAS-STING Pathway in Cancer.

TL;DR: mounting evidence now suggests that depending on the context, cGAS-STING signaling can also have tumor and metastasis-promoting functions, and its chronic activation can paradoxically induce an immune-suppressive tumor microenvironment.
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Intratumor Heterogeneity: The Rosetta Stone of Therapy Resistance

TL;DR: The sources of intratumor heterogeneity and approaches to capture and account for it during clinical decision making are discussed and potential strategies to improve therapeutic outcomes by directly targeting intrumor heterogeneity are outlined.
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Context is everything: aneuploidy in cancer

TL;DR: The context dependency of aneuploidy in cancer is explained and its clinical potential is discussed, which may have clinical relevance as a prognostic marker and as a potential therapeutic target.
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Inflammatory microenvironment remodelling by tumour cells after radiotherapy.

TL;DR: How radiotherapy, through its immunomodulating effects, represents a promising combination partner with ICIs and how DNA damage response inhibitors in combination with radiotherapy may be used to further augment this approach are described.
References
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Inflammation and cancer

TL;DR: It is now becoming clear that the tumour microenvironment, which is largely orchestrated by inflammatory cells, is an indispensable participant in the neoplastic process, fostering proliferation, survival and migration.
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Genetic instabilities in human cancers

TL;DR: There is now evidence that most cancers may indeed be genetically unstable, but that the instability exists at two distinct levels, and recognition and comparison of these instabilities are leading to new insights into tumour pathogenesis.
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The Immune Landscape of Cancer

TL;DR: An extensive immunogenomic analysis of more than 10,000 tumors comprising 33 diverse cancer types by utilizing data compiled by TCGA identifies six immune subtypes that encompass multiple cancer types and are hypothesized to define immune response patterns impacting prognosis.
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Cyclic GMP-AMP Synthase is a Cytosolic DNA Sensor that Activates the Type-I Interferon Pathway

TL;DR: Results indicate that cGAS is a cytosolic DNA sensor that induces interferons by producing the second messenger cGAMP, which belongs to the nucleotidyltransferase family.
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STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling.

TL;DR: The identification of a molecule (STING; stimulator of interferon genes) that appears essential for effective innate immune signalling processes is reported, implying a potential role for the translocon in innate signalling pathways activated by select viruses as well as intracellular DNA.
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