Targeting Survivin May Enhance Chemotherapy Efficacy in Retinoblastoma


YM155 combined with chemotherapy shows promise reducing retinoblastoma cells and tumors in mouse models.

A recent study found that an inhibitor of the protein survivin called YM155 combined with chemotherapy provides a superior treatment for retinoblastoma (Rb).

Survivin is a protein that prevents cell death.

The study, published in PLOS One, examined whether chemotherapy agents such as carboplatin and topotecan induced a pro-survival phenotype associated with increased expression of survivin in Rb cells and tumors in mouse models.

Researchers found exposure to chemotherapy agents resulted in higher levels of survivin in 2 human Rb cell lines, however, it was not observed in normal ocular retinal pigmented epithelial (RPE) cells.

Researchers also found that exposure to YM155 significantly decreased levels of survivin in Rb cells, but not in RPE cells.

A combination of YM155 and chemotherapy agents was the most effective in resulting Rb cell death when compared to either alone, the study reported.

Researchers then used the combination of YM155 and chemotherapy agents in mouse models with tumors in their eyes.

The same positive results were found using YM155 combined with carboplatin.

"Our study shows proof of concept, that we can enhance chemotherapeutic approaches to retinoblastoma while using the same dosage," said Charles Gomer, PhD, lead author of the study. "We're hopeful that following additional preclinical studies that this combination therapy will offer better outcomes to children with retinoblastoma and perhaps the possibility of reduced chemotherapy, reducing long-term adverse effects."

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