A new marker already linked to other types of cancer was found to play a role in the most common childhood primary tumor inside the eye, researchers at the University of Michigan Health System have found. Their findings were published by Khan et al in Laboratory Investigation.
Retinoblastoma is a rare form of cancer affecting the retina. When advanced forms of retinoblastoma affect both eyes, this cancer causes partial or full loss of vision in about 50% of patients. This tumor is normally treated by eye removal or administration of chemotherapy—often toxic to the normal retina, thus jeopardizing vision. No targeted therapy exists for this type of cancer.
A team of researchers led by Rajesh Rao, MD, Assistant Professor of Ophthalmology and Visual Sciences and Pathology at the University of Michigan Medical School, found that the novel marker EZH2 selectively marks retinoblastoma tumor cells but not normal retinal cells. EZH2 is an enzyme that controls how other genes function to promote cell growth. It is normally expressed in the retina during fetal development but shuts off after birth.
In contrast, Dr. Rao and his colleagues found that retinoblastoma tumors express EZH2 at high levels, even after birth. Their team found in laboratory experiments that EZH2 inhibitors, a new class of drug that is already in use in clinical trials against other cancers, targeted retinoblastoma tumor cells but not nontumor retinal cells.
“This work identifies one of the first new markers for retinoblastoma in many years and points toward the possibility that a treatment currently in clinical trials may be a future, targeted therapy for children with this disease,” said Dr. Rao.
The researchers will next seek to better understand how EZH2 works in retinoblastoma and begin to test EZH2 inhibitors in animal models of retinoblastoma in the laboratory. If their findings are positive, the researchers could begin exploring possibilities for a clinical trial to test the possibility of using an EZH2 inhibitor—already in trials for other types of cancer—for retinoblastoma.
This study was supported by the National Eye Institute, Beat Blindness, Research to Prevent Blindness, and the Knights Templar Eye Foundation.
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