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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?.
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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 Tumor Time Cancer cell
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
NK Using Natural Killer Cells (NK) to target ovarian cancer 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 CA125 MUC16 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 Antibody Hemoglobin MUC16
Why is CA125 Detected in the Blood? CA125 CA125 CA125 Ovarian Cancer cell
Why is CA125 Detected in the Blood? Blood CA125 CA125 CA125 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 CA125 CA125 CA125 Ovarian Cancer cell Cell Death
Importance of MUC16 (CA125) in Ovarian Cancer NK CA125 CA125 CA125 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
MUC16medium MUC16high MUC16low NK cells selectively target csMUC16low cells
MUC16 binds to NK cells Blood vessel NK NK Ovarian Cancer cell
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
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
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