Identifications of genetic and epigenetic targets to improve cancer therapies

Thesis

Cancer remains a global health burden. Despite advances in our understanding of cancer biology and the development of cancer treatments, including radiotherapy, chemotherapy, hormonal therapy, targeted therapy, and immunotherapy, persistent limitations in efficacy due to tumour heterogeneity, therapy resistance, and immune evasion underscore the need for developing novel cancer therapies.

This thesis presents an integrated approach to identify and characterise new genetic and epigenetic targets for cancer therapy. Firstly, we identified UDP-xylose synthase 1 (UXS1) as a novel genetic target in non-small cell lung cancer (NSCLC) cells with high expression of UDP-glucose dehydrogenase (UGDH), revealing a metabolic vulnerability with therapeutic potential. We also identified type I protein arginine methyltransferases (PRMTs) as epigenetic targets capable of enhancing T cell function, providing a potential strategy to improve adoptive cell transfer therapies. Finally, we elucidated novel mechanistic insights into lysine-specific demethylase 1 (LSD1), a known cancer therapy target, and explored its functional interplay with metabolic pathways.

Collectively, these findings advance our understanding of cancer biology and identify therapeutic targets across genetic and epigenetic domains. The work provides a foundation for developing novel cancer therapies that address current limitations.

Authors: Wang, Y

• DOI: 10.5287/ora-zrwxzmyj1
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: epigenetics; cancer therapy; genetics
• Subjects: Cancer