CA125: More than Just a Biomarker Manish S. Patankar, PhD University of Wisconsin-Madison Department...
-
Upload
dina-thompson -
Category
Documents
-
view
215 -
download
1
Transcript of CA125: More than Just a Biomarker Manish S. Patankar, PhD University of Wisconsin-Madison Department...
![Page 1: CA125: More than Just a Biomarker Manish S. Patankar, PhD University of Wisconsin-Madison Department of OB/GYN Division of Gynecologic Oncology.](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649cda5503460f949a48ea/html5/thumbnails/1.jpg)
CA125: More than Just a Biomarker
Manish S. Patankar, PhDUniversity of Wisconsin-Madison
Department of OB/GYNDivision of Gynecologic Oncology
![Page 2: CA125: More than Just a Biomarker Manish S. Patankar, PhD University of Wisconsin-Madison Department of OB/GYN Division of Gynecologic Oncology.](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649cda5503460f949a48ea/html5/thumbnails/2.jpg)
• What is CA125?
• Why is CA125 detected in the blood of cancer patients?
• Why do ovarian cancer cells produce CA125?
![Page 3: CA125: More than Just a Biomarker Manish S. Patankar, PhD University of Wisconsin-Madison Department of OB/GYN Division of Gynecologic Oncology.](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649cda5503460f949a48ea/html5/thumbnails/3.jpg)
Ovarian Cancer Cell Under an Electron Microscope
27-30 micrometer
![Page 4: CA125: More than Just a Biomarker Manish S. Patankar, PhD University of Wisconsin-Madison Department of OB/GYN Division of Gynecologic Oncology.](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649cda5503460f949a48ea/html5/thumbnails/4.jpg)
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
![Page 5: CA125: More than Just a Biomarker Manish S. Patankar, PhD University of Wisconsin-Madison Department of OB/GYN Division of Gynecologic Oncology.](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649cda5503460f949a48ea/html5/thumbnails/5.jpg)
TumorCancer cell Time
Diagnosis and treatment
![Page 6: CA125: More than Just a Biomarker Manish S. Patankar, PhD University of Wisconsin-Madison Department of OB/GYN Division of Gynecologic Oncology.](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649cda5503460f949a48ea/html5/thumbnails/6.jpg)
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
![Page 7: CA125: More than Just a Biomarker Manish S. Patankar, PhD University of Wisconsin-Madison Department of OB/GYN Division of Gynecologic Oncology.](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649cda5503460f949a48ea/html5/thumbnails/7.jpg)
Using Natural Killer Cells (NK) to target ovarian cancer
Cancer cell
NK
NK
Cell Death
![Page 8: CA125: More than Just a Biomarker Manish S. Patankar, PhD University of Wisconsin-Madison Department of OB/GYN Division of Gynecologic Oncology.](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649cda5503460f949a48ea/html5/thumbnails/8.jpg)
Cancer cell
NK
NK cells attack cancer cells
![Page 9: CA125: More than Just a Biomarker Manish S. Patankar, PhD University of Wisconsin-Madison Department of OB/GYN Division of Gynecologic Oncology.](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649cda5503460f949a48ea/html5/thumbnails/9.jpg)
Boosting the anti-cancer activity of NK cells
Cancer cell
NK
NK
• huKS-IL2
• Resveratrol
![Page 10: CA125: More than Just a Biomarker Manish S. Patankar, PhD University of Wisconsin-Madison Department of OB/GYN Division of Gynecologic Oncology.](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649cda5503460f949a48ea/html5/thumbnails/10.jpg)
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
![Page 11: CA125: More than Just a Biomarker Manish S. Patankar, PhD University of Wisconsin-Madison Department of OB/GYN Division of Gynecologic Oncology.](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649cda5503460f949a48ea/html5/thumbnails/11.jpg)
• 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
![Page 12: CA125: More than Just a Biomarker Manish S. Patankar, PhD University of Wisconsin-Madison Department of OB/GYN Division of Gynecologic Oncology.](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649cda5503460f949a48ea/html5/thumbnails/12.jpg)
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
![Page 13: CA125: More than Just a Biomarker Manish S. Patankar, PhD University of Wisconsin-Madison Department of OB/GYN Division of Gynecologic Oncology.](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649cda5503460f949a48ea/html5/thumbnails/13.jpg)
What is CA125?CA125 is a tiny part of a very large molecule called MUC16
Ovarian Cancer cell
CA125
CA125
CA125
MUC16
![Page 14: CA125: More than Just a Biomarker Manish S. Patankar, PhD University of Wisconsin-Madison Department of OB/GYN Division of Gynecologic Oncology.](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649cda5503460f949a48ea/html5/thumbnails/14.jpg)
MUC16 Under an Electron Microscope
Mol. Wt= 3-10 million Da
1-2 mm in length
Courtesy of Dr. John Sheehan, U. North Carolina
![Page 15: CA125: More than Just a Biomarker Manish S. Patankar, PhD University of Wisconsin-Madison Department of OB/GYN Division of Gynecologic Oncology.](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649cda5503460f949a48ea/html5/thumbnails/15.jpg)
Mo
lecu
lar
size
Hemoglobin Antibody MUC16
![Page 16: CA125: More than Just a Biomarker Manish S. Patankar, PhD University of Wisconsin-Madison Department of OB/GYN Division of Gynecologic Oncology.](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649cda5503460f949a48ea/html5/thumbnails/16.jpg)
Why is CA125 Detected in the Blood?
Ovarian Cancer cell
CA125
CA125
CA125
![Page 17: CA125: More than Just a Biomarker Manish S. Patankar, PhD University of Wisconsin-Madison Department of OB/GYN Division of Gynecologic Oncology.](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649cda5503460f949a48ea/html5/thumbnails/17.jpg)
Why is CA125 Detected in the Blood?
Ovarian Cancer cell
CA125
CA125
CA125
Blood
![Page 18: CA125: More than Just a Biomarker Manish S. Patankar, PhD University of Wisconsin-Madison Department of OB/GYN Division of Gynecologic Oncology.](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649cda5503460f949a48ea/html5/thumbnails/18.jpg)
Serum CA125 Assay
CA125
![Page 19: CA125: More than Just a Biomarker Manish S. Patankar, PhD University of Wisconsin-Madison Department of OB/GYN Division of Gynecologic Oncology.](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649cda5503460f949a48ea/html5/thumbnails/19.jpg)
• 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
![Page 20: CA125: More than Just a Biomarker Manish S. Patankar, PhD University of Wisconsin-Madison Department of OB/GYN Division of Gynecologic Oncology.](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649cda5503460f949a48ea/html5/thumbnails/20.jpg)
Ovarian Cancer cell
CA125
CA125
CA125
Importance of MUC16 (CA125) in Ovarian Cancer
Cell Death
![Page 21: CA125: More than Just a Biomarker Manish S. Patankar, PhD University of Wisconsin-Madison Department of OB/GYN Division of Gynecologic Oncology.](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649cda5503460f949a48ea/html5/thumbnails/21.jpg)
Ovarian Cancer cell
CA125
CA125
CA125
Importance of MUC16 (CA125) in Ovarian Cancer
No Cell Death
![Page 22: CA125: More than Just a Biomarker Manish S. Patankar, PhD University of Wisconsin-Madison Department of OB/GYN Division of Gynecologic Oncology.](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649cda5503460f949a48ea/html5/thumbnails/22.jpg)
Ovarian Cancer cell
Importance of MUC16 (CA125) in Ovarian Cancer
Cell Death
NK
NK
![Page 23: CA125: More than Just a Biomarker Manish S. Patankar, PhD University of Wisconsin-Madison Department of OB/GYN Division of Gynecologic Oncology.](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649cda5503460f949a48ea/html5/thumbnails/23.jpg)
MUC16 Protects Ovarian Cancer Cells from NK cells
Ovarian Cancer
Ovarian Cancer
NK
NK
![Page 24: CA125: More than Just a Biomarker Manish S. Patankar, PhD University of Wisconsin-Madison Department of OB/GYN Division of Gynecologic Oncology.](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649cda5503460f949a48ea/html5/thumbnails/24.jpg)
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
![Page 25: CA125: More than Just a Biomarker Manish S. Patankar, PhD University of Wisconsin-Madison Department of OB/GYN Division of Gynecologic Oncology.](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649cda5503460f949a48ea/html5/thumbnails/25.jpg)
MUC16 binds to NK cells
NK
Ovarian Cancer cell
NK
Blood vessel
![Page 26: CA125: More than Just a Biomarker Manish S. Patankar, PhD University of Wisconsin-Madison Department of OB/GYN Division of Gynecologic Oncology.](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649cda5503460f949a48ea/html5/thumbnails/26.jpg)
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
![Page 27: CA125: More than Just a Biomarker Manish S. Patankar, PhD University of Wisconsin-Madison Department of OB/GYN Division of Gynecologic Oncology.](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649cda5503460f949a48ea/html5/thumbnails/27.jpg)
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
![Page 28: CA125: More than Just a Biomarker Manish S. Patankar, PhD University of Wisconsin-Madison Department of OB/GYN Division of Gynecologic Oncology.](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649cda5503460f949a48ea/html5/thumbnails/28.jpg)
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
![Page 29: CA125: More than Just a Biomarker Manish S. Patankar, PhD University of Wisconsin-Madison Department of OB/GYN Division of Gynecologic Oncology.](https://reader035.fdocuments.in/reader035/viewer/2022062515/56649cda5503460f949a48ea/html5/thumbnails/29.jpg)