Ovarian cancer is the deadliest gynaecological cancer in the world, with around 1,800 cases diagnosed in Australia annually, reaching nearly a quarter of a million cases worldwide. Treatment for ovarian cancer has largely stayed the same in the past 30 years, with an increasing number of cases becoming resistant to current therapies. Due to its asymptomatic early stages and lack of an early detection biomarker, most ovarian cancer patients are diagnosed at a later stage where the survival rate is very low. Therefore, more effort into finding an early detection biomarker and better drugs to treat therapy-resistant ovarian cancer is required.
It is known that epigenetics plays a vital role in cancer development and progression. Circular RNAs (circRNAs) are a recently identified group of non-coding RNAs that can act as epigenetic regulators in cancer development. They have potential utility in biomarker development due to their tissue-specific expression and increased stability compared to their cognate linear RNAs. We identified circular RNAs that are dysregulated in ovarian cancer using long-read sequencing and developed a highly sensitive digital PCR assay that can detect these dysregulated circular RNAs in very small amounts of ovarian cancer patient plasma. Furthermore, we are characterising the functions of these dysregulated circular RNAs in therapy resistance, oncogenesis, and metastasis by utilising circRNA overexpression and knockdown approaches. Successful completion of this project will lead to the development of an accurate early detection biomarker and novel circular RNA therapeutic targets that can effectively treat chemoresistant ovarian cancer.