New tumour suppressor gene discovered
Cancer Research UK funded researchers have discovered a gene that is switched off in around one per cent of all cancers and could hold a vital clue to new treatments.
The scientists from the Wellcome Trust Sanger Institute in Cambridge found that inactivation of the gene - called CUX1 - triggers a biological pathway that increases tumour growth.
"This genetic fault could play an important role in more than 3,000 cancers diagnosed every year in the UK" - Dr Emma Smith, Cancer Research UK
Drugs currently in development that block this pathway could lead to a new therapy for people whose tumours have the inactivated gene.
Dr David Adams, a Cancer Research UK scientist at the Wellcome Trust Sanger Institute, said: "Our research is a prime example of how understanding the genetic code of cancers can drive the search for targeted cancer therapies that work more effectively and efficiently. This could improve the lives of thousands of people suffering from cancer."
Using genetic data from 7,600 cancer patients through the International Cancer Genome Consortium (ICGC), researchers showed that around one in every 100 tumours had DNA faults that inactivated CUX1.
While these faults only happen in a small proportion of tumours, they occur in many different cancers.
Dr Chi Wong, first author from the Wellcome Trust Sanger Institute, said: "Our work harnesses the power of combining large-scale cancer genomics with experimental genetics.
"CUX1 defects are particularly common in myeloid blood cancers. As these patients have a dismal prognosis currently, novel targeted therapies are urgently needed."
The team silenced CUX1 in cells grown in the laboratory to understand how switching it off might lead to the development of tumours.
They found that when CUX1 is deactivated, it had a knock-on effect on a biological inhibitor called PIK3IP1, which reduced its inhibitory effects.
This in turn mobilised an enzyme that contributes to cell growth, called phosphoinositide 3-kinase (PI3K), increasing the rate of tumour progression.
Professor Paul Workman of the Institute of Cancer Research, London, said: "Drugs that inhibit PI3K signalling are currently undergoing clinical trial. This discovery will help us to target these drugs to a new group of patients."
Dr Emma Smith, senior science information officer at Cancer Research UK, said: "This type of research paints a more detailed picture of the genes that may increase the risk of developing different types of cancer. And this will be key in helping scientists find and target changes that underpin the disease.
"This genetic fault could play an important role in more than 3,000 cancers diagnosed every year in the UK - further research might help develop new tests to identify patients who will benefit from drugs that target the mistake. This takes us a step closer to more personalised treatment that could help to boost survival rates."
The research is published in the journal Nature Genetics.
Copyright Press Association 2013
- Wong C.C, et al. (2013). Inactivating CUX1 mutations promote tumorigenesis, Nature Genetics, DOI: 10.1038/ng.2846