There are few treatment options for women with advanced endometrial cancer, which often relapses after developing resistance to chemotherapy. Now, however, new research suggests that targeting a protein that is most abundant on cancer stem cells in endometrioid tumors may offer a way forward.
woman with a doctor
Researchers in Ohio may have just found a new potential drug target for treating endometrial cancer.

In the Journal of Experimental Medicine, researchers from the Cleveland Clinic in Ohio explain how they investigated the immune regulatory protein CD55 and the role that it plays in cancer stem cells in endometrioid tumors.

Endometrial, or uterine, cancer is a disease that mainly affects women after the menopause. It arises when cells of the inner lining of the uterus, or the endometrium, grow out of control.

In the United States, endometrial cancer is the most commonly diagnosed cancer of the reproductive system in women.

The Cleveland Clinic team explains that, as in ovarian cancer, uterine cancer has four tumor subtypes, depending on the tissue involved. The tumor subtypes are endometrioid, serous, mucinous, and clear cell carcinoma.

Over 80 percent of uterine cancers are endometrioid carcinomas. This subtype also contributes to around 15 percent of epithelial ovarian cancers, which is cancer that starts in the tissue surrounding the ovary.

Need for new treatments

For the past 25 years, the standard treatment for women with endometrial or ovarian cancer has been surgery to remove cancerous tissue, and chemotherapy with the platinum-based drug cisplatin.

However, while the treatment may at first achieve remission, the cancer often returns and develops resistance to the chemotherapy, leaving women with few treatment options.

The new study focuses on cancer stem cells, precursor cells that are thought to be the main drivers of recurrence and spread in many cancer types.

If these cells develop resistance to treatment, then while tumors may respond and shrink at first, within a few months, the cancer is back.

After studying laboratory-grown human cells and tissue from patients, the researchers found an abundance of CD55 protein on the surface of cancer stem cells in endometrioid tumors.

Blocking CD55 may restore susceptibility

The researchers found that high levels of CD55 protein in the stem cells of the endometrioid tumors made the cells more aggressive and caused them to develop resistance to cisplatin.

Using cultured cells and mouse models, they found that removing CD55 from the cancer stem cells made them succumb to cisplatin.

The authors explain that to effectively neutralize cancer stem cells, both their ability to self-renew and their ability to resist chemotherapy need to be addressed. However, these two processes are often controlled by separate molecular pathways.

The new study is significant because it shows how targeting CD55 may offer a way to block both self-renewal and treatment-resistance in the stem cells of endometrioid tumors.

The researchers suggest that blocking CD55 may offer a way to increase the effectiveness of cisplatin chemotherapy. It may also be possible to use the protein as a marker for certain aggressive gynecologic cancers.

After they finish the preclinical testing, they plan to run a clinical trial in patients with endometrial cancers that express CD55.

Endometrial cancer is the most common gynecologic malignancy in the United States, yet research in this area is understudied and underfunded. We hope that our study will lead to much needed new therapy options for women with treatment resistant, relapsed disease.”

Study co-leader Dr. Ofer Reizes, Cleveland Clinic