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CA125: More than Just a Biomarker Manish S. Patankar, PhD University of Wisconsin-Madison Department of OB/GYN Division of Gynecologic Oncology • What is CA125? • Why is CA125 detected in the blood of cancer patients? • Why do ovarian cancer cells produce CA125? Ovarian Cancer Cell Under an Electron Microscope 27-30 micrometer How small are cancer cells? Diameter of a penny is 19.05 millimeter or 19,050 micrometer The diameter of a cancer cell is approximately 1/700th-1/600th of a penny Diagnosis and treatment Cancer cell Time Tumor Research at University of Wisconsin-Madison • Understanding the biological role of CA125 in ovarian cancer • Developing immunotherapeutic agents that target ovarian cancer • Developing novel therapeutic agents that can inhibit the growth of cancer cells Using Natural Killer Cells (NK) to target ovarian cancer NK NK Cancer cell Cell Death NK cells attack cancer cells NK Cancer cell Boosting the anti-cancer activity of NK cells • huKS-IL2 • Resveratrol NK NK Cancer cell Boosting the anti-cancer activity of NK cells • huKS-IL2: Increases the ability of NK cells to bind to cancer cells • Resveratrol activates NK cells NK Cancer cell Cell Death New therapeutic agents •Conjugated Linoleic acid (CLA) •A constituent of milk and red meat •CLA inhibits growth of ovarian cancer cells when tested under experimental conditions Research at University of Wisconsin-Madison • Understanding the biological role of CA125 in ovarian cancer • Developing immunotherapeutic agents that target ovarian cancer • Developing novel therapeutic agents that can inhibit the growth of cancer cells What is CA125? CA125 is a tiny part of a very large molecule called MUC16 MUC16 CA125 CA125 CA125 Ovarian Cancer cell MUC16 Under an Electron Microscope Mol. Wt= 3-10 million Da 1-2 mm in length Courtesy of Dr. John Sheehan, U. North Carolina Molecular size Hemoglobin Antibody MUC16 Why is CA125 Detected in the Blood? Ovarian Cancer cell Why is CA125 Detected in the Blood? Blood Ovarian Cancer cell Serum CA125 Assay CA125 •CA125 is not useful for early detection of ovarian cancer •Used only for follow-up •Study from an European trial (MRC OV05/EORTC 55955) suggest that early treatment of recurrent cancer determined by rise in CA125 does not result in benefit in survival of patients Importance of MUC16 (CA125) in Ovarian Cancer Ovarian Cancer cell Cell Death Importance of MUC16 (CA125) in Ovarian Cancer Ovarian Cancer cell No Cell Death Importance of MUC16 (CA125) in Ovarian Cancer NK NK Ovarian Cancer cell Cell Death MUC16 Protects Ovarian Cancer Cells from NK cells Ovarian Cancer NK Ovarian Cancer NK NK cells selectively target csMUC16low cells MUC16medium MUC16low MUC16high Number of conjugates 40 30 20 10 0 csMUC16low csMUC16medium csMUC16high MUC16 binds to NK cells NK Blood vessel NK Ovarian Cancer cell Loss of MUC16 Increases Survival of Ovarian Cancer Bearing Mice 110 100 90 80 70 60 50 40 30 20 10 0 Percent survival MUC16 MUC16 0 50 100 150 Days 200 pos neg 250 -OVC -OVC 300 Introduce NK cells to target tumors Introduce agents that inhibit production of MUC16 (CA125) Ovarian Tumor Decrease in MUC16 (CA125) will •Induce cancer cell death •Disarm the cells and allow targeting by NK cells Our Team • Dr. Arvinder Kapur, Dr. Rebecca Whelan, Mildred Felder, Kai Ludwig, Soma Banerjee, and Yang Liu • Drs. David Kushner, Ellen Hartenbach, Laurel Rice, Steve Rose, Ahmed Al-Niami • Drs. Nonyem Onujiogu, Mian Shahzad, Shitanshu Uppal • Drs. Paul Sondel, Paul Campagnola, Pamela Kreeger, Arthur Polans, and Irwin Goldman