Cancer arises from progressive acquisition of alterations in DNA of cells. Knowledge of these alterations has led to groundbreaking discoveries in targeted therapies for some cancers such as Herceptin which targets over-produced HER2 proteins in HER2-positive breast cancer. However, identifying targeted therapeutic approaches for treating ovarian cancer remains in its infancy. One challenge is that tumors from ovarian cancer patients contain thousands of DNA alterations, making it difficult to identify causal genes critical for cancer development and progression. This proposal has applied a high-throughput screening approach to analyze gene function in cancer genomes, aiming to identify cancer-causing genes with therapeutic potential in ovarian cancer.
Preliminary studies revealed 17 candidate genes that were able to transform non-cancer cells into cancerous cells and often over-produced in primary ovarian tumors. Furthermore, we confirmed the top candidate GAB2 signaling protein to be over-produced in at least 44% of primary ovarian tumors. Patients whose tumors are GAB2-positive showed poor prognosis. This proposal will investigate the cancer-causing ability and therapeutic potential of these 17 genes in ovarian cancer. This proposal will also test hypotheses that over-produced GAB2 proteins promote the aggressive growth of ovarian tumors, and in response to chemotherapy, enable tumor cells to survive and re-grow rapidly as resistant tumors.
Hiu Wing (Tony) Cheung, Ph.D., is currently an Assistant Professor in the Department of Pathology and Laboratory Medicine at the Medical University of South Carolina and an associate member at the Hollings Cancer Center. Dr. Cheung obtained his B.Sc. in Biochemistry, M.Phil., and Ph.D. from the University of Hong Kong, where he received an outstanding graduate student award and Croucher Foundation fellowship. Dr. Cheung pursued postdoctoral training in the laboratory of Dr. William Hahn at the Dana-Farber Cancer Institute and Broad Institute of M.I.T. and Harvard in Boston, where he studied the mechanisms of oncogene-driven malignant transformation of ovarian cancer using high-through screening tools such as RNA interference library. Dr. Cheung’s current research interests focus on studying ovarian cancer genomes to elucidate the mechanisms of tumor development, progression and tumor recurrence, with an emphasis on identifying novel therapeutic targets to improve treatment. In addition to the Ovarian Cancer Research Fund Liz Tilberis grant, Dr. Cheung’s work has been supported by multiple awards, including The V Foundation for Cancer Research V Scholar Award and the Marsha Rivkin Center for Ovarian Cancer Research Pilot Study Award.