Yale Research on the Detection and Early Treatment of Ovarian Cancer

With support from The Honorable Tina Brozman Foundation, a team at Yale has been working on strategies for the early detection and treatment of ovarian cancer.  Those strategies include the development of biomarkers that can be used for screening, identifying the early precursors of the cancer, and developing new therapies that will block tumor growth at an early stage and prevent recurrence, metastasis, and resistance to chemotherapy.

The work on biomarkers resulted in a test called OvaSure that had been marked in the United stated until late 2008, when the FDA said it needed more testing information to license the test.  LabCorp, the company that marketed OvaSure, is working with the FDA to obtain permission to market the test again.  OvaSure continues to be available in Israel and it is expected to be available in Italy and Denmark in early 2010.

In the meantime, the Yale team continues to conduct further studies of the test.  For example, they started a longitudinal study with 110 high risk individuals.  The team already detected to cases of early stage ovarian cancer.  If funds become available in the future, that study might be expanded.

With support from The Honorable Tina Brozman Foundation, a research fellow has been working on identifying the early precursors of ovarian cancer. Recurrence is a major problem with ovarian cancer and is the cause of mortality.  The Yale team is conducting innovative research that may hold the key to preventing metastatic disease.   Most first-year medical students know that a cancer cell is one that divides very quickly and divides without control. Current chemotherapy is usually effective because it destroys these fast growing cells.  But the challenge for clinicians comes from the fact that almost 90% of women with ovarian cancer relapse within 5 years, even with the best treatment. Why is that?

The work being done at Yale University suggests that ovarian cancer cells are not as homogeneous as we once thought. When these cells are cultured, the researchers at Yale find that most cells divide very quickly, but others quite slowly.  In the past, researchers have assumed that the fast dividing cells were the ones to concentrate on when looking for effective chemotherapeutic agents.  But the researchers at Yale decided to focus more on the slow growing cells.  As a result, they discovered that the slow growing cells have all the molecular characteristics of adult stem cells (see photograph below).

A brief review of stem cell physiology will shed some light on why this discovery is so important:
If you cut your skin, it’s not epithelial cells that heal the wound but rather adult stem cells in the area of the wound are able to produce epithelial cells to replace the damaged cells.  In simple terms, one reason humans look the same over the years is because these stem cells have a memory of what we look like.

Similarly, the Yale team has isolated stem cells that have a memory of cancer cells.  So they asked: What if the cells responsible for cancer recurrence are actually stems cells with a good memory?  To use an analog, these cancer-like stem cells can be compared to an army’s generals and the fast dividing cells to the foot soldiers.  Traditional chemotherapy has proven effective in destroying the fast growing soldiers but the generals remain behind to generate new soldiers.

They believe that these stem cells represent the source of  reoccurrence and metastasis.  When they cloned these stem cells to understand their molecular characteristics, they discovered that the impetus that causes the stem cells to generate more “soldiers” is tissue damage.  In other words, when you kill cancer cells, a message is sent to these stem cells: “You need to repair this organ,” much the same as when normal stem cells receive the message to repair a damaged skin cell.  That would explain why chemotherapy can shrink a tumor by 35% only to have it grow back three weeks later.

So determining whether such stem cells are present after surgery is critical to determine the best type of treatment!  The Yale team recently completed a study in which they found that if a patient, even though she has localized stage 1 and 2, has a high percentage of the cancer stem cells, the cancer is much more likely to recur. They are currently screening for therapeutic agents that would target these cancer stem cells.  They are looking for a therapeutic agent that will block this repair process. So far they have 2 compounds that they think will accomplish that goal and suppress cancer stem cells. While the data to date are in vitro and animal data, the next stage will be early clinical trials.

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The Honorable Tina Brozman Foundation is a section 501(c)(3) charitable organization.