Transcript Document

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