Elucidation of the high-grade serous ovarian cancer acetylome to identify novel therapeutic vulnerabilities

Abstract

Ovarian cancer is a deadly disease that quietly develops asymptomatically. There are many types of ovarian cancer. The subtype of ovarian cancer depends on the disease origin, histology and cell type. High-grade serous is the deadliest and most aggressive form of ovarian cancer. Currently FDA approved treatment options are limited and often result in the development of drug resistance. This has led to the investigation of alternative treatment opportunities. Histone deacetylase (HDAC) proteins are a group of proteins involved in many cellular processes through their modulation of the acetylation post-translational modification. Their overexpression has been associated with poor prognosis and chemoresistance in high-grade serous ovarian cancer (HGSOC). The development of HDAC inhibitors has been investigated for their utility in solid tumor cancers, including ovarian cancer. However, much remains unknown surrounding the benefit of targeting HDACs in HGSOC treatment. In this thesis, we employed an array of mass spectrometry-based proteomic approaches to improve our understanding of HDACs and the function of their inhibitors in HGSOC. This thesis highlights the potential of HDAC proteins as a treatment target but emphasizes future work that needs to be done to advance current treatment modalities.