Identification of novel therapeutic targets for ovarian cancer using large-scale RNAi functional screening = Identification of novel therapeutic targets for ovarian cancer using large-scale RNAi functional screening

다국어 초록 (Multilingual Abstract)

Ovarian cancer is the most challenging disease in gynecologic malignancy with the poor prognosis even after comprehensive treatment. We aimed to explore new therapeutic targets by using pathological and clinical features of ovarian cancer as biomarkers. As a method of finding suitable therapeutic target molecules, we focused on high-throughput screening, which is a technique for selecting targets from enormous types of subjects using automated robots. We set following two features of ovarian cancer as biomarkers.
(1) Gene amplification or over-expression of c-Myc was observed in 30-60% in ovarian cancer.
(2) Cisplatin resistance was frequently confirmed in ovarian cancer.
I: Precision medicine in ovarian cancer
Synthetic lethal action refers to a phenomenon that does not show lethality with a single gene deficiency but exerts cell death when multiple gene defects coexist. The concept of synthetic lethality has been used to treat ovarian cancer. Focusing on gene alterations and histologic type, we’d like to discuss about precision medicine in ovarian cancer.
II: Identification of novel therapeutic target for ovarian cancer using RNAi functional screening High throughput screening was conducted in a specialized facility using RNAi library consisted of drug target molecules and MicroRNAs.
(1) High expression of c-Myc
We searched for new therapeutic targets specific to ovarian cancer cells using high expression of c-Myc as a biomarker. Two ovarian cancer cell lines which have similar growth rates but different expression levels of c-Myc were selected and subjected to large-scale siRNA screening using the 6550 gene library.
(2) Cisplatin resistance
Cisplatin resistance greatly influences the prognosis of ovarian cancer. Therefore, large-scale siRNA screening considering cisplatin resistance as a biomarker was performed using a cisplatin-resistant ovarian cancer cell line. By comparing the cell viability of cisplatin added (IC20) and non-added groups, a group of genes that cancels cisplatin resistance by siRNA functional inhibition were extracted.