Metastasis in ovarian cancer is the main obstacle for the successful treatment of patients with ovarian cancer and the main cause of their death. Emerging evidence suggests that a disruption in the structure of the epithelial cells of the ovary leads to cancer cell metastatis. In his study, Dr. Chien will study the molecular steps involved in changing the physical structure of ovarian cancer cells. The results from this study could provide insights into biological processes underlying metastatic tumor progression, and could lead to the identification of those tumors with particularly metastatic and aggressive behavior.
BioAssistant Professor, Cancer Biology Assistant Director, Translational Genomics, University of Kansas Cancer Center Ph.D.: Reproductive Physiology, University of Kansas Medical Center, Kansas City, Kan. Postdoctoral: Tumor Biology, Mayo Clinic, Rochester, Minn.
Research FocusCancer Genomics, Cancer Therapeutics, Translational Genomics, Ovarian Cancer
The primary objective of my research program is to understand the genetic basis of ovarian cancer and to translate this knowledge into clinical applications in the early detection and the treatment of ovarian cancer. To support this objective, my current research focuses on three areas:
- Genomics of ovarian cancer: Although genetic alterations are considered as a hallmark of cancer, specific genetic alterations serve as "drivers" in cancer progression while others are considered "passenger" mutations. Advances in the identification of "driver" genetic alterations in cancer will lead to the development of novel therapeutic targets to effectively treat cancer, and it is a prerequisite in the era of "Personalized Medicine" or "Precision Cancer Medicine." My research focuses on the characterization of genetic mutations from cancer genomes to identify driver mutations in ovarian cancer. I apply various approaches in functional genetics, genomics, and bioinformatics to identify somatic mutations (single nucleotide variants, insertions and deletions, translations, fusion transcripts, copy number alterations) and aberrantly expressed genes (that are associated with clinical outcomes) to elucidate the genetic basis of ovarian cancer.
- Development of genome-based biomarkers for early detection of ovarian cancer. Recent studies by the Cancer Genome Atlas identifies TP53 mutations in 95% of high-grade serous ovarian cancer. Almost universal nature of TP53 mutations in this disease inspires us to test whether these mutations serve as biomarkers for diagnosis and detection of high-grade serous ovarian cancer. We are applying emerging PCR methods and next-generation sequencing technologies to identify low-level TP53 mutations in patient samples so that these genomics assays may later be translated as clinical assays in the diagnosis of early-stage ovarian cancer.
- Development of targeted therapies for advanced-stage ovarian cancer. The Cancer Genome Atlas studies also identifies FoxM1 as a candidate gene that is overexpressed in 84% of high-grade serous ovarian cancer. High levels of FoxM1 expression in this disease suggest it may serve as a therapeutic target, analogous to Her2 in breast cancer, Abl in leukemia, and Braf in melanoma serving as therapeutic targets in respective diseases. We are evaluating two antibiotics and an experimental therapeutic agent to characterize their cytotoxic activity in ovarian cancer cells and to understand how these agents are affecting FoxM1 expression and inducing cytotoxic effects in cancer cells. Ultimately, we plan to exploit genetic vulnerabilties in ovarian cancer by identifying synthetic lethal interactions and by developing therapeutic combinations that cause synthetic lethality in ovarian cancer.