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An investigation of the engagement of cGAS-STING signaling upon DNA damage in cancer cells
thesisposted on 2023-06-21, 05:45 authored by SUMAIAH SAEED A AL ASMARI
When cancer cells undergo DNA damage, leakage of DNA to the cytoplasm can triggers an immune response which can be both anti-and pro-tumorigenic. This response relies on a pathway called the cGAS-STING pathway. Although this pathway is known to have anti-cancer properties, it can also produce pro-inflammatory and pro-tumorigenic factors that promote cancer growth. In this PhD project, we found that inhibiting the cGAS-STING pathway can reduce the production of pro-tumorigenic factors in some cancer cells. We also discovered that inhibiting downstream modulators of NF-κB signaling, such as ERK1/2, could help limit inflammation while retaining anti-proliferative effects. Additionally, we found that inhibiting the extracellular secretion of 2'3' cGAMP could also reduce inflammation. These findings suggest new strategies for improving cancer treatment.
Principal supervisorMichael Gantier
Additional supervisor 1Bryan Williams
Year of Award2023
Department, School or CentreCentral Clinical School
Additional Institution or OrganisationMolecular and Translational Science (Hudson Institute)
CourseDoctor of Philosophy
FacultyFaculty of Medicine, Nursing and Health Sciences