Unmet NeedOvarian cancer is the most common cause of death among gynecological cancers and is associated with poor outcomes and low overall survival rates. The current standard of care involves surgical resection of the solid tumor, followed by chemotherapy. This type of therapy has limited success among women with advanced disease, and often results in recurrence. Advances in new ovarian cancer therapies have been limited due largely to a lack of understanding of the molecular characteristics of the disease. As such, there is a need for a more comprehensive understanding of the underlying epigenetics of ovarian cancer in order to facilitate the development of new, more effective therapeutic treatments.
Technology OverviewJohns Hopkins researchers have developed a novel approach called, Trellis, for detecting and characterizing tumor-specific sequences and structural alterations in ovarian cancer by performing genome-wide sequencing analysis. Integrating these techniques with methylation and gene expression analyses has allowed for identification of molecular and genetic alterations associated with ovarian cancer. These studies identified alterations not previously implicated in ovarian cancer, such as the amplification, underexpression, deletion, and rearrangements of several specific genes and pathways.
Researchers further evaluated the effects of targeted agents on identified pathways using dose-response models. Such studies showed that ovarian tumors with PIK3CA and PPP2R1A alterations, which are common in ovarian clear cell cancers, showed enhanced sensitivity to PI3K inhibitors, suggesting that these inhibitors may be an effective therapeutic strategy. Evaluation of MYC amplification revealed that MYC plays a central role in multiple ovarian cancer cell lines and causes increased sensitivity to PARP inhibitors, suggesting a potential therapeutic target for this subset of ovarian cancers. These models may reveal new and effective treatment methods for ovarian cancer.
Stage of DevelopmentHopkins investigators have successfully identified molecular alterations associated with ovarian cancer, and further predicted and evaluated their susceptibility to targeted therapies. These studies reveal potential therapeutic targets for the treatment of ovarian cancer. Presently, all studies have been performed in vitro, and have evaluated only genomic, epigenomic, and transcriptomic changes. Future studies will also target proteomic, metabolomics, and carbohydrate changes to further characterize the condition. Additionally, in vivo studies will be needed to demonstrate the potential for clinical translation of these observations.
PublicationsPapp, E, et al. Cell Rep 25(9), 2617-2633, 2018.
