Ovarian cancer is the number one killer among all gynecologic cancers in women. Although chemotherapy is initially successful in reducing tumor growth, more than 60% of patients experience relapse within the first five years. Additional chemotherapy is rarely effective in patients with relapsed tumors. Our study of 798 patients showed that patients who have elevated levels of 10 specific biomarkers have a shorter survival time. Interestingly, all 10 biomarkers are involved in one common biological process: the formation of a collagen matrix around cancer cells. We will focus on two of these biomarkers, COL11A1 and POSTN, because they are the most abundantly expressed during ovarian cancer progression.
COL11A1 and POSTN are produced by cells that infiltrate tumors in a similar way that blood vessels penetrate deep into tumor tissue to provide nutrients for cancer cells. In addition to delivering nutrients and growth factors, these infiltrating cells are thought to secrete a thick collagen-rich matrix that protects cancer cells from the lethal effect of chemotherapy and serves as an incubator for increasingly aggressive cancer cells. In the proposed project, we will study how this collagen-rich environment formed by COL11A1 and POSTN changes cancer cell behavior. We will also test the therapeutic effects of preventing the formation of a collagen matrix in cancer cells using inhibitors of COL11A1 and POSTN. We believe that this study will promote the development of a novel class of drugs that will overcome chemotherapy-resistance and prevent cancer progression, thereby providing clinicians with a more effective approach to treat patients diagnosed with ovarian cancer.
This grant was made possible by a donation from the UC Office of the President Tobacco-Related Disease Research Program.
Dong-Joo (Ellen) Cheon, Ph.D., is currently a postdoctoral fellow in the Women’s Cancer Program at the Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center (Los Angeles, CA) under the mentorship of Dr. Sandra Orsulic. Dr. Cheon earned her B.S. and M.S. from Seoul National University (Seoul, Korea) and a Ph.D. from the University of Texas M.D. Anderson Cancer Center (Houston, TX). Her doctoral studies focused on the in-vivo functions of the ovarian cancer antigen, CA125/MUC16, in embryonic development and ovarian cancer. She joined Dr. Orsulic’s laboratory in 2009 to study the role of a collagen-remodeling gene signature in ovarian cancer metastasis and chemo-resistance. Dr. Cheon is interested in the molecular mechanisms underlying metastatic cancer progression and chemo-resistance as well as the development of novel therapeutic strategies to improve patient survival outcome. Dr. Cheon has received several awards, including the Ache-Murray Fellowship for Ovarian Cancer Research and the Schissler Foundation Fellowship in Genetics of Human Disease.