Abstract 3068: Hedgehog signaling regulates drug sensitivity by targeting ABC transporters in epithelial ovarian cancer (EOC)

A major challenge of successful chemotherapy in treatment of ovarian cancer is overcoming intrinsic or acquired multi-drug resistance caused mostly by the active efflux mediated by ATP-binding cassette (ABC) transporters. The regulation of these transporters in ovarian cancer is poorly understood. Our research shows that in ovarian cancer, abnormal regulation of the hedgehog (Hh) signaling pathway is involved in regulation of ABC transporters. Hh is a known regulator of cancer cell proliferation and differentiation in several other types of invasive and metastatic malignancies. Our work on Gli1, a key Hh downstream signaling gene, has shown frequent activation of the Hh pathway in ovarian cancer. Inhibition of the Hh signaling pathway by inhibitors or Gli1 siRNA increases ABC gene expression levels and the response of ovarian cancer cells to certain chemotherapeutic drugs. The mechanism underlying is a direct association of Gli1 with a specific consensus sequence located in the promoter region of ABC genes. This study provides new information in the knowledge of ABC gene regulation and will contribute to generating new targets/markers to detect and anticipate ovarian cancer patient chemotherapy drug sensitivity which could lead to more effective treatments and improved survival. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3068. doi:1538-7445.AM2012-3068