Researchers used CRISPR to find a pair of genes that show strong potential as a new therapeutic target for uveal melanoma – a rare eye cancer.
Researchers used CRISPR to find a pair of genes that show strong potential as a new therapeutic target for uveal melanoma – a rare eye cancer.
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New research has found a novel target with therapeutic potential for metastatic eye melanoma — an aggressive eye cancer — with implications for a range of other cancers.
Published today (4 July) in Nature Genetics, scientists from the Wellcome Sanger Institute and their collaborators used CRISPR screening — a gene-editing tool — to reveal two genes, CDS1 and CDS2, which strongly rely on each other in metastatic eye melanoma. This could pave the way for more targeted and effective cancer treatments, which are currently lacking.
This research advances the scientific understanding of gene targets for a range of cancers but also may provide a hopeful outlook for eye cancer patients with very limited therapeutic options.
Uveal melanoma is a rare but deadly cancer with up to 600 patients diagnosed each year across the UK.1 There are only four sites across the UK which treat this type of cancer. The treatment options for patients are invasive and include having their eye surgically removed or receiving radiation therapy to the eye. Whilst these treatments are successful and cancer recurrences in the eye rarely happen, approximately half of all patients will go on to develop metastatic disease in the liver within two to three years.2,3
To help address the need for more alternative treatment options, scientists from the Sanger Institute and their collaborators sought to better understand the genetics of uveal melanoma cells.
In a new study, the researchers used a gene-editing tool called CRISPR-Cas9,4 which enables precise changes to DNA, in order to identify single genes and gene pairs that are essential for the cancer cells to survive and grow. Using CRISPR-Cas9 screening in 10 human uveal melanoma cell lines,5 the researchers knocked out — or “turned off” — genes individually and in pairs to look for lethal genetic interactions, also known as synthetic lethal pairs.
The researchers identified 76 genes that individually are essential to uveal melanoma and 105 gene pairs that interact lethally when disrupted together.
“We need better options to treat uveal melanoma. To make progress, it’s vital for researchers to understand more about the disease on a molecular level. That’s why it’s promising to see the results of this work, uncovering detailed elements of the biology behind the disease and opening up new opportunities to beat it. This discovery could now pave the way to new, targeted treatments in the future, not just for uveal melanoma, but also for other cancer types.”
Dr Anna Kinsella, Research Information Manager at Cancer Research UK
Credit: The Welcome Sanger Institute