Scientists have identified a gene that is responsible for the development of tumours in one per cent of all cancer patients.
The culprit is CUX1, which when deactivated allows a “biological pathway” to open up that causes tumour growth to increase.
Researchers already knew about CUX1 but not that it was a driver of cancer because it mutates at a low frequency compared to other genes that mutate at a high rate and therefore were the focus of previous studies.
The aim now is to develop drugs that inhibit the biological pathway responsible for accelerating the tumour growth to treat patients with this type of cancer-causing mutation.
The research, which was published this week in Nature Genetics, was based on genetic data from over 7,600 cancer patients, collected and sequenced by the International Cancer Genome Constortium (ICGC) and other groups.
This Youtube clip explains the research findings:
More detail from the press release:
“Our work harnesses the power of combining large-scale cancer genomics with experimental genetics,” says Dr Chi Wong, first author from the Wellcome Trust Sanger Institute and practising Haematologist at Addenbrooke’s Hospital. “CUX1 defects are particularly common in myeloid blood cancers, either through mutation or acquired loss of chromosome 7q. As these patients have a dismal prognosis currently, novel targeted therapies are urgently needed.”
“Data collected from large consortia such the ICGC, provides us with a new and broader way to identify genes that can underlie the development of cancers,” says Professor David Tuveson from Cold Spring Harbor Laboratory. “We can now look at cancers as groups of diseases according to their tissues of origin and collectively examine and compare their genomes.”
The team silenced CUX1 in cultured cells to understand how inactivating it might lead to the development of tumours. They found that when CUX1 is deactivated, it had a knock-on effect on a biological inhibitor, PIK3IP1, reducing its inhibitory effects. This mobilises an enzyme responsible for cell growth, phosphoinositide 3-kinase (PI3K), increasing the rate of tumour progression.
The team has already identified several dozen other genes that when mutated at a low frequency could promote cancer development. They plan to silence these genes in mice to fully understand how their inactivation may lead to cancer development and the mechanisms by which this occurs.
“Drugs that inhibit PI3K signalling are currently undergoing clinical trial,” says Professor Paul Workman, Deputy Chief Executive and Head of Cancer Therapeutics at The Institute of Cancer Research, London. “This discovery will help us to target these drugs to a new group of patients who will benefit from them and could have a dramatic effect on the lives of many cancer sufferers.”