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Spread of deadly eye tumour cells stemmed in fish

A new drug that suppresses the spread of tumour cells in zebra fish could pave the way for future treatments of childhood eye cancer.

By blocking a ‘domino effect’ that causes the cancerous cells to multiply, researchers from Johns Hopkins University believe there is renewed hope for treating retinoblastoma – a cancer which originates in the retina, affecting up to 8,000 children per year, killing 4,000.

“There is no effective treatment for retinoblastoma that spreads,” Dr Laura Asnaghi, a research associate faculty member in the Department of Pathology at the Johns Hopkins University School of Medicine, said.

“However, there is a chance for us to treat this deadly cancer if caught early before the tumours spread. Therefore, we looked into the causes for the tumour invasion, which can help us develop targeted therapies to prevent invasion.”

For the study, the US-based research team compared the RNA profiles of two groups of childhood eye tumour patients – invasive and non-invasive. The profiles revealed that RNA levels for the gene that codes for the activin A receptor were 2–3x higher in invasive retinoblastoma cells.

Zebrafish eye injected with retinoblastoma tumor cells (green) form a mass in areas close to the injection site. A few of these tumor cells move outside the eye.
Zebrafish eye injected with retinoblastoma tumor cells (green) form a mass in areas close to the injection site. A few of these tumor cells move outside the eye.

With the activin receptor gene already known to have a role in other cancers, researchers considered it could be a key target for suppressing cancer spread and growth in retinoblastoma.

The activin receptor typically detects a growth signal, triggering cells to grow and divide, however, the researchers used a drug to block the receptor from detecting the signals. Results showed that the growth, proliferation and invasion of retinoblastoma cells treated with the drug were suppressed by 60–80%.

The scientists then injected human retinoblastoma cells into embryonic zebra fish, which possess an underdeveloped immune system that couldn’t reject the cells.

Treating the cancer cells with the same drug, they discovered a 55% reduction in the diameter of eye tumours compared to zebra fish eyes not injected with the drug.

Asnaghi said the experiments showed blocking the activin receptor could be effective in suppressing the growth and spread of invasive retinoblastoma cells in people.

“We hope our findings will provide new therapies for retinoblastoma, and lead to preserving vision and improving outcomes in a greater number of children affected by retinoblastoma,” she said.

“We are cautiously optimistic though, because we need to do more research before any related therapies can be safely developed or tested for patients.”

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