For the past 25 years, standard therapy for endometrial and ovarian cancers has included surgery and the chemotherapy drug cisplatin. While these treatments typically are initially successful, the cancer often recurs and becomes resistant to cisplatin, leaving patients with limited treatment options.
A research team led by Justin Lathia, PhD, and Ofer Reizes, PhD, both of the Department of Cellular and Molecular Medicine, studied the unique role of an immune regulatory protein called CD55 which is abundant on the surface of endometrioid ovarian cancer cells and uterine cancer cells. Using human cells and patient-derived tissue models, they found CD55 to be the most prevalent on cancer stem cells, a subgroup of aggressive cancer cells that are thought to be responsible for recurrence and spread of many types of cancer.
The researchers discovered that high levels of CD55 caused cancer stem cells to be more aggressive and resistant to cisplatin than non-stem cell cancer cells. The CD55 pathway is unique in that it controls both stem cell self-regulation and growth and therapeutic resistance, while other mechanisms control just one or the other.
In addition, when CD55 was removed from cells, they became sensitive to cisplatin in cell culture models and in pre-clinical mouse models. The researchers hope that blocking the protein will enhance cisplatin treatments and that high expression of CD55 can be used as a biological marker of aggressive gynecologic cancers. The team plans to complete further preclinical testing followed by a clinical trial in patients with CD55-expressing endometrial cancers.
Research fellow Caner Saygin, MD, was first author on this study, which is published in the Journal of Experimental Medicine. Dr. Reizes holds the Laura J. Fogarty Endowed Chair for Uterine Cancer Research at Cleveland Clinic.