MENUResearchers discover marker for rare but lethal eye cancer
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Could lead to potential treatment target using new class of drugs currently being tested in other cancer
ANN ARBOR, Mich. — 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 Michigan Medicine have found.
Retinoblastoma is a rare but lethal form of cancer. When advanced forms of RB affect both eyes, this cancer causes partial or full loss of vision in about 50 percent of patients. This tumor is normally treated by eye removal or administration of chemotherapy drugs that are often toxic to the normal retina, and thus can jeopardize vision. No targeted therapy, which selectively kills tumor cells but spares normal retinal cells, exists.
A team of researchers led by Rajesh Rao, M.D., 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 while the retina is growing during fetal development, but it shuts off after birth.
In contrast, 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 non-tumor 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," says Rao, assistant professor of ophthalmology and visual sciences and of pathology at the University of Michigan Medical School.
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 lab. 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.
The study was published in Laboratory Investigation.
Note to patients: EZH2 inhibitors are not currently being used to treat retinoblastoma and no clinical trials are currently planned.
Additional authors: Mehnaz Khan, Laura L. Walters, Qiang Li, Dafydd G. Thomas, Jason M.L. miller, Qitao Zhang, Andrew P. Sciallis, Yu Liu, Brian J. Dlouhy, Patrice E. Fort, Steven M. Archer, Hakan Demirci, Yali Dou.
Funding: National Eye Institute grants K12 EY022299 and T32 EY,013934 Beat Blindess, Research to Prevent Blindness, Knights Templar Eye Foundation.
Disclosure: None.
Reference: Laboratory Investigation, published online Aug. 17, 2015, doi: 10.1038/labinvest.2015.104.