CA125: More than Just a Biomarker
Manish S. Patankar, PhDUniversity of Wisconsin-Madison
Department of OB/GYNDivision 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
TumorCancer cell Time
Diagnosis and treatment
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
Cancer cell
NK
NK
Cell Death
Cancer cell
NK
NK cells attack cancer cells
Boosting the anti-cancer activity of NK cells
Cancer cell
NK
NK
• huKS-IL2
• Resveratrol
Boosting the anti-cancer activity of NK cells
Cancer cell
NK
• huKS-IL2: Increases the ability of NK cells to bind to cancer cells
• Resveratrol activates NK cells
Cell Death
• Conjugated Linoleic acid (CLA)
• A constituent of milk and red meat
• CLA inhibits growth of ovarian cancer cells when tested under experimental conditions
New therapeutic agents
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
Ovarian Cancer cell
CA125
CA125
CA125
MUC16
MUC16 Under an Electron Microscope
Mol. Wt= 3-10 million Da
1-2 mm in length
Courtesy of Dr. John Sheehan, U. North Carolina
Mo
lecu
lar
size
Hemoglobin Antibody MUC16
Why is CA125 Detected in the Blood?
Ovarian Cancer cell
CA125
CA125
CA125
Why is CA125 Detected in the Blood?
Ovarian Cancer cell
CA125
CA125
CA125
Blood
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
Ovarian Cancer cell
CA125
CA125
CA125
Importance of MUC16 (CA125) in Ovarian Cancer
Cell Death
Ovarian Cancer cell
CA125
CA125
CA125
Importance of MUC16 (CA125) in Ovarian Cancer
No Cell Death
Ovarian Cancer cell
Importance of MUC16 (CA125) in Ovarian Cancer
Cell Death
NK
NK
MUC16 Protects Ovarian Cancer Cells from NK cells
Ovarian Cancer
Ovarian Cancer
NK
NK
MUC16low MUC16medium MUC16high
NK cells selectively target csMUC16low cells
csMUC16low csMUC16medium csMUC16high0
10
20
30
40
Nu
mb
er o
f co
nju
gat
es
MUC16 binds to NK cells
NK
Ovarian Cancer cell
NK
Blood vessel
Loss of MUC16 Increases Survival of Ovarian Cancer Bearing Mice
0 50 100 150 200 250 3000
102030405060708090
100110
MUC16 neg -OVCMUC16 pos -OVC
Days
Per
cen
t su
rviv
al
Introduce agents that inhibit production of MUC16 (CA125)
OvarianTumor
Decrease in MUC16 (CA125) will
• Induce cancer cell death
• Disarm the cells and allow targeting by NK cells
Introduce NK cells to target tumors
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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