Characterization of therapeutic strategies for the treatment of ARID1A-deficient pancreatic cancer

by Maira Volland
Doctoral thesis
Date of Examination:2024-11-05
Date of issue:2024-10-29
Advisor:Prof. Dr. Elisabeth Hessmann
Referee:Prof. Dr. Elisabeth Hessmann
Referee:Prof. Dr. Matthias Dobbelstein
Persistent Address: http://dx.doi.org/10.53846/goediss-10821

 

 

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Abstract

English

Pancreatic ductal adenocarcinoma (PDAC) is characterized by great molecular heterogeneity, with a large number of epigenetic factors playing a central role in addition to known genetic changes such as the KRAS mutation. Due to the high diversity, an individualized therapy adapted to the genotype and phenotype appears to offer a promising opportunity. The aim of this study was to understand the tumour biological consequences and therapeutic vulnerabilities of pancreatic cancer subtypes characterized by a loss of expression of ARID1A (AT-rich interactive domain-containing protein 1A). ARID1A is a subunit of the SWI/SNF chromatin remodeling complex, which frequently shows inactivating mutations in PDAC. Preliminary work shows that the loss of ARID1A promotes PDAC progression.
Keywords: PDAC; epigenetic; targeted therapy; ARID1A