Targeting the Bromodomain-containing protein 4 in ovarian clear cell carcinoma

• Main Author: Wong, Erica Shiyi
• Other Authors: Vinay Tergaonkar
• Format: Final Year Project
• Language: English
• Published: 2017
• Subjects: DRNTU::Science
• Online Access: http://hdl.handle.net/10356/70625
• Institution: Nanyang Technological University

Ovarian clear cell carcinoma (OCCC) is the second most common histopathological subtype of ovarian carcinoma (OC), making up 5-25% of all OC. Current treatment utilizing combination chemotherapy with cisplatin and paclitaxel have low efficacy with a 5-year survival rate of only 12%. Bromodomain-containing protein 4 (BRD4) is known to be upregulated in OCCC and is also involved in many cancer progression pathways, thus making it an important therapeutic target. Additionally, there are reported cases of OCCC gaining resistance to BRD4 inhibitor treatment, which may be due to adaptive kinome reprogramming. Thus, this study aims to elucidate the role of BRD4 in OCCC, as well as identify potential alternative combination therapies involving BRD4 and kinase inhibitors to combat OCCC. ShRNA-mediated BRD4 knockdown (KD) cells were generated and cell proliferation, migration and invasion assays performed. The study found that cell proliferation, migration and invasion capabilities were reduced in BRD4 KD cells, implying that BRD4 plays an important role in tumour growth and metastasis. CRISPR/Cas9 mediated BRD4 knockout (KO) cells are currently being generated for screening of kinase inhibitor libraries. It is hoped that this would lead to identification of potential combination therapies for OCCC.