NCRI 2015

Four molecular subtypes identified in pancreatic cancer

Dr David Chang - University of Glasgow, Glasgow, UK

What I will be presenting will be based on our findings as part of the pancreatic cancer sequencing project of the International Cancer Genome Consortium and a couple of little stories from there, the first one being using the whole genome sequencing to define the mutational landscape of pancreatic cancer and also define a DNA damage repair defective molecular phenotype that those patients preferentially respond to DNA damaging agents. So that’s the first story and the second story is something that we’ve submitted recently that’s under revision on the integrated analysis of the 450 cancer genomes that we’ve sequenced. The major finding of that is we are finding four major molecular subtypes of pancreatic cancer based on the different gene transcription programmes as well as the prognosis as well as also where we think we might be able to use these gene programmes that we’re presenting each subtype to better help us elucidate and to find out different novel mechanisms that we could target.

Such as potential targets for new drugs?

Even just to rationalise the drugs that we have on the market, number one. Or, yes, potentially new drugs that can be used to target a particular pathway or a particular sort of over-activity in a subtype of the cancer.

Is this the first time that pancreatic cancer has been split up in this way?

For the DNA damage repair defective phenotype it has been shown, which we know for a while already in breast and ovarian cancer, that they preferentially respond to DNA damaging agents. For pancreatic cancer there were some signals in previous clinical trials but this was probably the first time that we were able to explain it genomically. This particular signature is also now being inferred not just in breast, ovarian, pancreatic, it has now also been shown in gastric cancer as well which was just recently published, not by us but by the group.

What main points does your presentation highlight?

First of all, pancreatic cancer is quite heterogeneous genomically. It probably is dauntingly heterogeneous that when you first look at it you think, ‘OK, where are we going to start? How are we going to tackle this?’ But using the different ways of analysing these genomes we should be able to group the similarities together and then they should tackle them from that fashion rather than going straight down to thinking that there’s no way of breaking this disease. So that’s probably number one; conclusion number two that I will also present is some of our recent experience in personalised medicine in pancreatic cancer which was a feasibility study that we conducted in Australia before we moved to Glasgow to show people what real life personalised therapy in pancreatic cancer looks like. It’s not simple, there are a lot of obstacles but we’ve learned a lot from it which I will share with the audience and also will bring up something called PRECISION-Panc. It’s a research and treatment platform that we want to set up here in the UK as a platform that we could bring forward to bring the committee together to see how we could tackle this daunting disease really.

What has the trial shown you so far?

We’ve learned that these patients are usually… because the setting of the trial, the inclusion criteria of the trial is that the patient has to be in the metastatic setting, meaning that they can deteriorate very fast, so a rapid turnaround of molecular information is probably the most crucial thing. We found that we were able to return the information, 75% of the patients with the information, within four weeks. But even then we still see a good proportion of patients who later on become not eligible for the trial because they either passed away in that period of time while they’re waiting for the results to come back or their performance status actually deteriorates so much that they’re no longer fit enough to receive any more chemotherapy. So a rapid turnaround time and a good communication between the molecular multidisciplinary team and the treating oncologist are the keys that we’ve learned.