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CA125: More than Just a Biomarker

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?.

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CA125: More than Just a Biomarker

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  1. CA125: More than Just a Biomarker Manish S. Patankar, PhD University of Wisconsin-Madison Department of OB/GYN Division of Gynecologic Oncology

  2. What is CA125? • Why is CA125 detected in the blood of cancer patients? • Why do ovarian cancer cells produce CA125?

  3. Ovarian Cancer Cell Under an Electron Microscope 27-30 micrometer

  4. 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

  5. Diagnosis and treatment Tumor Time Cancer cell

  6. 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

  7. NK Using Natural Killer Cells (NK) to target ovarian cancer NK Cancer cell Cell Death

  8. NK cells attack cancer cells NK Cancer cell

  9. Boosting the anti-cancer activity of NK cells • huKS-IL2 • Resveratrol NK NK Cancer cell

  10. 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

  11. 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

  12. 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

  13. What is CA125? CA125 is a tiny part of a very large molecule called MUC16 CA125 MUC16 CA125 CA125 Ovarian Cancer cell

  14. MUC16 Under an Electron Microscope Mol. Wt= 3-10 million Da 1-2 mm in length Courtesy of Dr. John Sheehan, U. North Carolina

  15. Molecular size Antibody Hemoglobin MUC16

  16. Why is CA125 Detected in the Blood? CA125 CA125 CA125 Ovarian Cancer cell

  17. Why is CA125 Detected in the Blood? Blood CA125 CA125 CA125 Ovarian Cancer cell

  18. Serum CA125 Assay CA125

  19. 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

  20. Importance of MUC16 (CA125) in Ovarian Cancer CA125 CA125 CA125 Ovarian Cancer cell Cell Death

  21. Importance of MUC16 (CA125) in Ovarian Cancer NK CA125 CA125 CA125 Ovarian Cancer cell No Cell Death

  22. Importance of MUC16 (CA125) in Ovarian Cancer NK NK Ovarian Cancer cell Cell Death

  23. MUC16 Protects Ovarian Cancer Cells from NK cells Ovarian Cancer NK Ovarian Cancer NK

  24. MUC16medium MUC16high MUC16low NK cells selectively target csMUC16low cells

  25. MUC16 binds to NK cells Blood vessel NK NK Ovarian Cancer cell

  26. 110 100 pos MUC16 -OVC 90 neg MUC16 -OVC 80 70 60 Percent survival 50 40 30 20 10 0 0 50 100 150 200 250 300 Days Loss of MUC16 Increases Survival of Ovarian Cancer Bearing Mice

  27. Introduce agents that inhibit production of MUC16 (CA125) Introduce NK cells to target tumors Ovarian Tumor • Decrease in MUC16 (CA125) will • Induce cancer cell death • Disarm the cells and allow targeting by NK cells

  28. 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

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