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ertems@mskcc.org Therapeutic Targeting of Cancer Stem Cells in Metastatic Tumors
Epithelial ovarian cancer, an incurable disease, is the fourth leading cause of cancer-related deaths in women in the United States. While most patients initially respond to surgery and chemotherapy, they inevitably relapse and become refractory to chemotherapy with the more aggressive tumors being associated with metastasis into the abdomen and eventual death from resistant disease. Cancer stem cells (CSCs) provide a reservoir of cells that can self-renew, and generate differentiated cells that make up the bulk of the tumor. They are particularly resistant to most therapeutic modalities and may be the primary source of recurrence. Improvements in cancer therapy require development of drugs that target CSC.
Dr. Ertem has discovered a novel cellular structure consisting of a chain of cells which he termed “catena” (Latin for “chain”) in the abdominal metastasis of human ovarian cancer. His experiments showed that any single catena cell can form a rapidly growing ovarian cancer tumor in immunodeficient mice, suggesting that catenae are composed exclusively of ovarian cancer stem cells. This discovery is regarded as a major advance in cancer stem cell research. He has developed an in vitro cell culture system to indefinitely expand ovarian cancer stem cells as a pure population in catenae. This system is unique in that it allows isolation and extensive expansion of CSC under conditions where all the cells remain as CSC without differentiating, yet retain differentiation potential.
The catena was initially discovered in ovarian cancer although the results could apply to several other metastatic cancers such as breast cancer, lung cancer, colon cancer, and cervical cancer.
The catena cell culture system allows establishment of a complete biological profile of ovarian cancer stem cells and also for the first time provides a unique model for testing compounds that can selectively target cancer stem cells. While platinums and taxanes have been profoundly helpful in extending survival, these drugs have not altered the cure rate. This strategy of separating CSC’s, delineating their biology and identifying novel therapeutics might achieve curative therapy. Furthermore, for the first time, this system allows identification of specific biomarkers for cancer stem cells with the potential to be used for early detection of cancers.
