Roles and Applications of cGAS/STING Signalling in Aneuploid Cancer

Bakker, Marco (2019) Roles and Applications of cGAS/STING Signalling in Aneuploid Cancer. Master's Thesis / Essay, Biomedical Sciences.

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Abstract

Aneuploidy is a hallmark of cancer and affects roughly two thirds of all cancers. Normally, the DNA is well confined inside the nucleus. However, chromosomal mis-segregation as a result of chromosomal instability can cause chromosomes to end up inside separate micronuclei, which are often fragile structures. DNA leakage into the cytosol is detected by cGAS, the catalyser for cGAMP synthesis. cGAMP activates STING, which promotes the production of type 1 interferons in a TBK1-dependent manner. Type 1 interferons are known to play a vital role in boosting both the innate as adaptive immune system, which could induce a more powerful antitumor immune response. However, cGAS/STING also features tumour-promoting abilities, such as inducing angiogenesis and metastasis. Therefore, it is highly under debate whether the cGAS/STING pathway acts as a tumour-suppressor or tumour-promotor. In this thesis, the positives and negatives of cGAS/STING signalling are put into consideration in attempt to clarify its role in aneuploid cancer. Due to cGAS/STING’s ability to facilitate an antitumor immune response, this thesis also aims to inquire a possible application of the pathway in a therapeutic setting, specifically in the enhancement of immune-checkpoint blockade-based immunotherapy.

Item Type:	Thesis (Master's Thesis / Essay)
Supervisor name:	Foijer, F.
Degree programme:	Biomedical Sciences
Thesis type:	Master's Thesis / Essay
Language:	English
Date Deposited:	22 Jul 2019
Last Modified:	23 Jul 2019 10:05
URI:	https://fse.studenttheses.ub.rug.nl/id/eprint/20389

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