Ovarian Cancer Research Highlights

Grantee: Pamela K. Kreeger, PhD
Institution: University of Wisconsin-Madison 
Focus Area: Mission Boost
Grant Term: 1/1/2019 to 12/31/2020

The Challenge: High-grade serous ovarian cancer (HGSOC) is the most common kind of ovarian cancer and begins growing in one of the fallopian tubes, which carry a woman’s egg from the ovaries to the uterus. HGSOC can quickly spread to another place in the body. Here’s how: Tumor cells break off from the first tumor and float through the fluid in the abdominal cavity, trying to attach to organs in the abdomen. 

The Research: With previous ACS grant funding, Pamela Kreeger, PhD, and her team figured out that some immune cells called macrophages can release a protein that HGSOC needs to spread. When abdominal organs interact with this protein, they make a sticky protein of their own. These two sticky proteins make it easier for the cancer cells floating in the fluid to attach to an organ or other body part and start a HGSOC tumor. Women with HGSOC have more of both these types of proteins in their body than women who don’t have HGSOC. 

Kreeger thinks that finding a way to stop the body from making these two proteins may stop HGSOC from spreading.

With new American Cancer Society funding from a Mission Boost Grant, Kreeger is studying a drug called maraviroc (sold under the brand name Selzentry) , which is used to treat certain types of HIV by targeting one of the proteins also found in HGSOC. Her aim is to determine if the drug slows the production of these proteins in mice with HGSOC in hopes that the cancer will grow more slowly or not come back at all. 

The Goal and Long-term Possibilities: If maraviroc works in mice, the next hopeful step would be to test it in women who have HGSOC in a clinical trial. Ultimately, Kreeger hopes maraviroc can help women with HGSOC live longer. 

Grantee: Mingfeng Bai, PhD*
Institution: Vanderbilt University Medical Center 
Focus Area: Cancer Drug Discovery
Grant Term: 7/1/2017 to 6/30/2021

The Challenge: Most cases of ovarian cancer are diagnosed at late stages when tumors have spread to other areas of the body. Treatment for ovarian cancer is usually surgery followed by chemotherapy. But sometimes cancer cells or tiny tumors are left behind after surgery. Some tumors may also resist chemotherapy, “refusing” to die. As a result, the cancer can return, often in less than 2 years, and for most women it is diagnosed at a late stage.

The Research: In his lab, Mingfeng Bai, PhD, is trying to develop a light-sensitive compound that binds to cancer cells. The goal is for the compound is to be especially attracted to ovarian cancer cells that are resistant to chemotherapy. Light will activate the compound to kill cancer cells.

Then Bai and his team plan to test the effectiveness of the compound on cells in the lab and then in mice. They expect few side effects because of the way they plan for the compound to target cancer cells and because should not be toxic without light. 

The Goal and Long-term Possibilities: If the treatment works well in mice, the next step would be to test it in women. Their ultimate goal is for any tumor cells still in the body to be destroyed by using the light on an endoscope to activate the drug inside the cells, thereby preventing the cancer from coming back and the need for more surgery.  

*Funded by Pennsylvania CEOs Against Cancer

Grantee: Matthias Stephan, MD, PhD* 
Institution: Fred Hutchinson Cancer Research Center
Focus Area: Leukemia, Immunology, and Blood Cell Development
Term: 7/1/2016 to 6/30/2020

The Challenge: CAR T-cell therapy requires re-engineering specific genes in a type of immune cell called T-cells. To create the treatment, a patient’s own T-cells are removed and sent to a lab, where they are changed by adding a man-made chimeric antigen receptor (CAR). Then those altered T-cells, with the added CAR, are injected back into the patient. The CAR helps the T-cells locate and destroy cancer cells.

The FDA has approved CAR T-cell drugs for certain blood cancers, but CAR T-cell drugs for solid tumors, like ovarian cancer, are only available in clinical trials. 

The Research: Matthias Stephan, MD, PhD, and his team are testing a new way to add a CAR to T-cells in mice with ovarian cancer. They’re using extremely tiny, atomic-size substances called nanoparticles to deliver genes to T-cells. That way, the re-engineering to add a CAR happens in the blood, not in a lab. The team hopes this technique may allow CAR-T treatment to start working faster than the current method.

Stephan and his team are also studying another type of programmed nanoparticle that they hope can identify different molecules on cancer cells.

In addition, the team is studying if nanoparticles can help deliver a genome editing system called CRISPR to stop the natural braking system of immune cells. They hope the nanoparticle-programmed T-cells show better results than the current method of CAR-T therapy.

The Goal and Long-Term Possibilities: In the future, the researchers hope doctors might be able to use a nanoparticle to treat cancer in certain people immediately, before the disease becomes advanced. 

*Funded by the HOPE Foundation

Grantee: Michael R. Wilson, PhD 
Institution: Michigan State University in East Lansing
Focus Area: Develop, Differentiation and Cancer
Term: 1/1/2018 to 12/31/2020

The Challenge: Some studies have suggested that having endometriosis may increase a woman’s risk for certain types of ovarian cancer. With endometriosis, some of the cells lining the inside of the uterus don’t shed during menstruation. Instead, those cells can migrate to, and grow in, other reproductive organs, including the ovary. However, there’s been little research that actually shows that cells from the uterus can start cancer in an ovary.

The Research: Michael R. Wilson, PhD, and his team want to learn how cells from the lining of the uterus to get to the ovary, as well as what causes those cells to become cancerous once they get there.

The team has genetically altered mice to have endometriosis and a type of ovarian cancer that is associated with endometriosis. Then, they take cells from the lining of the uterus in those mice and transfer them into healthy mice. They want to answer questions like: Do the cells from the lining of the uterus get “help” from other cells around them to move? Do the cells from the lining of the uterus go to the fallopian tubes first? Does the ovary do something to attract the cells from the lining of the uterus?  

To get answers, they’ll compare cells from the uterus, fallopian tubes, and ovaries of healthy mice with the cells from the mice with endometriosis-related ovarian cancer.    

The Goal and Long-Term Possibilities: Wilson’s team hopes to find biomarkers that will provide signs as to if ovarian cancers can come from the uterus. Ultimately, they want their work to lead to new ways to do surgery in women that could eventually help prevent ovarian cancer related to endometriosis.