Key points:
- Scientists from the Wellcome Sanger Institute and collaborators, including cell signalling experts at the Institute, have identified a new therapeutic target for the treatment of metastatic eye melanoma, an aggressive and difficult to treat eye cancer.
- The group at the Sanger used a genetic screen to identify a clear vulnerability in uveal melanoma cells when a protein called CDS2 is lost.
- The key discovery focuses on the genes CDS1 and CDS2, which work together in a way that has not been shown before. Both genes encode enzymes that are involved in phosphoinositide synthesis, which is essential in key cancer pathways including melanoma.
- Previous research from the Institute has described the loss of CDS2 in genetically engineered mouse cells and characterised its effect on phosphoinositide synthesis.
- It is hoped this latest research will stimulate efforts to target CDS2 in uveal melanoma and other tumour types with very low levels of CDS1.
A paper published today by researchers from the Wellcome Sanger Institute and their collaborators (Chan et al.,) identifies a protein called CDS2 as a novel drug target with therapeutic potential for metastatic eye (uveal) melanoma — an aggressive eye cancer — with implications for a range of other cancers.
The research aimed to identify essential genes for cell survival in human eye melanoma cell lines in order to develop more effective treatments.
Uveal melanoma is a rare but deadly cancer with up to 600 patients diagnosed each year across the UK.1 Treatment options are invasive but generally successful, however approximately half of all patients go on to develop metastatic disease in the liver within two to three years.2,3
The research led by the group of Dr David Adams at the Sanger Institute involved CRISPR-Cas9 gene editing to knock out — or ‘turn off’ — genes individually and in pairs to look for lethal genetic interactions, also known as synthetic lethal pairs, in 10 human uveal melanoma cell lines.
Amongst the 76 genes identified that individually are essential to uveal melanoma and 105 gene pairs that interact lethally when disrupted together, the approach highlighted a particular importance for the interaction between genes called CDS2 and CDS1. CDS2 usually works with CDS1, a closely related enzyme, to provide a robust route for the synthesis of a group of phospholipids called ‘phosphoinositides’, which are essential for many cell functions, including cancer cell growth.
Credit: Babraham Institute
This news item is adapted from a press release from the Wellcome Sanger Institute: New drug target for aggressive eye cancer discovered.