A new class of cancer drug which targets a faulty gene might be effective in treating some aggressive pancreatic cancers, researchers from Cancer Research UK’s Cambridge Research Institute and the Wellcome Trust Sanger Institute reported in the journal Nature.

Pancreatic cancer kills approximately 37,000 people in the USA and 8,000 in the UK every year. Even though survival rates have been steadily getting better, fewer than 20% of patients survive for at least 12 months after diagnosis, the authors explained.

In this study, the researchers demonstrated that in human cancer cells and mice, USP9x – a gene – switches off through chemical tags located on the surface of DNA.

Professor David Tuveson believes that 15% of all patients with pancreatic cancer may have this faulty gene, and that medications might be created which strip away the chemical tags. Put simply, it might be possible to create drugs to treat 15% of pancreatic cancer cases.

The gene has not been identified in traditional gene-hunting approaches, Tuveson explains, which only look at DNA sequence changes.

Prof. Tuveson said:

“The genetics of pancreatic cancer has already been studied in some detail, so we were surprised to find that this gene hadn’t been picked up before. We suspected that the fault wasn’t in the genetic code at all, but in the chemical tags on the surface of the DNA that switch genes on and off, and by running more lab tests we were able to confirm this.

Drugs which strip away these tags are already showing promise in lung cancer and this study suggests they could also be effective in treating up to 15 per cent of pancreatic cancers.”

In this study, scientists used a technique known as “sleeping beauty transposon system” to screen for genes that accelerate the growth of pancreatic tumors.

A transposable element (TE) is a piece of DNA (DNA sequence) that can self-transpose (change its relative position) within the genome of a single cell – i.e. it can hop about the cell’s DNA from one location to another, sometimes landing in the middle of the gene. If it lands in the middle, the gene can stop working.

They were able to screen for tumor suppressor genes that would usually protect against cancer, by introducing the sleeping beauty transposon into mice with cancer of the pancreas.

When the genes are working properly, they act as brakes, when they are faulty they start multiplying out of control.

The scientists have already discovered several genes association with pancreatic cancer with this approach. Surprisingly, the most common genetic fault was one with no prior association to any type of cancer.

Co-lead author Dr David Adams, said:

“The human genome sequence has delivered many new promising leads and transformed our understanding of cancer. Without it, we would have only a small, shattered glimpse into the causes of this disease. This study strengthens our emerging understanding that we must also look into the biology of cells to identify all the genes that play a role in cancer.”

Senior Science Information Manager at Cancer Research UK, Dr Julie Sharp, said:

“These results raise the posility that a class of promising new cancer drugs may be effective at treating some pancreatic cancers.

Fewer than 20 per cent of people survive pancreatic cancer for a year after diagnosis – a situation that has improved little in the last 20 years. Studies like this one are part of Cancer Research UK’s commitment to invest more in hard-to-treat cancers like pancreatic cancer, hopefully improving treatment to save more lives in the future.”

Written by Christian Nordqvist