Retinoblastoma spread stopped in cells and fish

November 28, 2018 Staff reporters

By comparing genetic sequences in the eye tumours of children whose cancers spread with tumours that didn’t spread, Johns Hopkins Medicine researchers say they have found new evidence that a domino effect in cells is responsible for the cancer spreading and that blocking part of the chain of events — which they successfully accomplished in zebra fish and human cells — may stop the growth and spread of the eye tumour cells.

The new findings, the researcher say, could lead to a treatment for the most common eye cancer in children — retinoblastoma — that originates in the retina. According to the World Health Organisation, the cancer affects an estimated 7,000–8,000 children and kills up to 4,000 worldwide each year.

“There is no effective treatment for retinoblastoma that spreads,” says Dr Laura Asnaghi, a pathology department researcher at the Johns Hopkins University medical school. “However, there is a chance for us to treat this deadly cancer if caught early before the tumours spread.”

The researchers compared the ribonucleic acid (RNA) profiles of five the patients who had invasive tumours and five who had tumours that were not invasive. They found a two- to threefold increase in RNA levels for the gene that codes for activin A receptor type 1C (ACVR1C) in invasive retinoblastoma cells, compared to noninvasive cells. The activin receptor gene is already known to have a role in other cancers, leading the researchers to consider whether the activin receptor could be a key target for suppressing cancer spread and growth in retinoblastoma.

Normally, when the activin receptor detects a growth signal, it triggers cells to grow and divide. The researchers treated cells with the drug SB505124, which blocks the activin receptor from detecting growth signals. Results showed that the growth, proliferation and invasion of retinoblastoma cells treated with the drug were suppressed by 60 to 80 percent.

The researchers then injected human retinoblastoma cells into 2-day-old zebra fish eyes and monitored the growth and spread of the cancer cells before administering the same drug (SB505124) in the zebra fish eyes, saying they saw a 55 percent reduction in the diameter of eye tumours compared to zebra fish eyes not injected with the drug.

Overall, Asnaghi says, the experiments show that 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. We are cautiously optimistic though, because we need to do more research before any related therapies can be safely developed or tested for patients.”