Thursday February 25 2016
Pancreatic cancer has very poor outcome rates
"Major insight into killer pancreatic cancer," BBC News reports, after research into pancreatic cancer identified four distinct subtypes. This discovery may lead to new treatments for this notoriously hard-to-treat condition.
Researchers carried out an analysis of the complete set of DNA of 456 pancreatic tumours, which had been surgically removed from patients.
They looked for mutations in different genes linked to different pathways to tumour development.
They say the tumours could be subdivided into four types. Knowing the type of cancer a patient has would help doctors to target it better with the most effective treatment.
The four types identified were:
- squamous – which are more aggressive and spread more quickly
- immunogenic tumours – which cause disruption of the immune system
- pancreatic progenitor tumours – which are triggered by errors in the cells that should guide the development of the pancreas
- aberrantly differentiated endocrine exocrine (ADEX) tumours – which also disrupt the normal development of the pancreas
Currently, only 20% of people diagnosed with pancreatic cancer live for more than a year.
However, the researchers say some people respond unexpectedly well to some treatments, which suggests that certain tumours are more likely to respond to certain treatments than others.
Treatments already in use or in development – such as treatments that help the body's immune system recognise and attack cancer cells – could be targeted better.
We now need to see studies that look at targeting subtypes of pancreatic cancer with promising treatments to see if the theory holds.
Where did the story come from?
The study was carried out by researchers from more than 40 institutions, from countries including Scotland, Australia, the US, Germany and Italy.
It was funded by a variety of government research grants, universities and charities, and was published in the peer-reviewed journal Nature.
You can read the study for free online, but you will have to pay if you want to download it or print it out.
One of the researchers declared a financial interest in the work through receiving royalty payments from a genetics company.
The study was covered well by the UK media, in varying degrees of depth. Most stories quoted the researchers commenting on the possible implications for treatment, but they rightly did not imply that the research amounted to a cure.
BBC News reported that the average survival time for people with the squamous form of the disease was four months. It is not clear where this figure comes from, as it does not seem to be in the research paper.
A graph in the paper seems to suggest half of the patients with this type of the cancer were still alive after 13.3 months (the median survival time). This was shorter than the other three forms of the cancer, as reported.
What kind of research was this?
This was an experimental study that used gene sequencing technology and computer analysis to look for patterns of genetic mutations in a range of pancreatic tumours.
The study did not test treatments for pancreatic cancer, so we don't know whether their hypothesis that certain treatments will work better on certain subtypes of cancer is true.
What did the research involve?
Researchers took samples of tumours from 382 patients on an Australian pancreatic cancer database.
They carried out whole genome sequencing on the samples, and added data from another 74 pancreatic cancers previously sequenced.
They looked for patterns in the types of mutations they saw and divided the tumours into four types.
In their analysis, the researchers looked for gene mutations and divided them into types, based on the cancer-causing mechanism the mutations were associated with.
They also looked for mutations known to be common in other types of cancer, as well as mutations known to either respond or not respond to certain treatments in other types of cancer.
They then used RNA sequencing to identify how tumours evolved through transcription errors. Transcription errors are, essentially, damage caused to DNA because a gene wasn't copied correctly.
What were the basic results?
The researchers said they found 32 genes that were "significantly mutated" in pancreatic cancer, which were linked to 10 "molecular mechanisms" for causing cancer.
After further analysis, they identified four subtypes of pancreatic tumour:
- squamous tumours – which included gene mutations also seen in some classes of breast, bladder, lung, and head and neck cancers; the researchers said these tumours are more aggressive and spread more quickly in pancreatic cancer
- pancreatic progenitor tumour – which involved errors in the transcription networks that tell pancreas cells how to develop
- ADEX tumours – a subtype of pancreatic progenitor tumours, where specific genes are upregulated (genes have an increase in gene expression, a term used to describe the influence the "information" contained in genes can have on a cellular level)
- immunogenic tumours – which involve disruption of immune networks that normally identify cancerous cells and protect against them
How did the researchers interpret the results?
The researchers said their results allow them to "infer differences in the molecular evolution of pancreatic cancer subtypes and identify opportunities for therapeutic development".
In other words, the different types of tumours seem to have different causes, and targeting these causes might point the way to better treatments.
In particular, they said it may be possible to target immunogenic tumours better: "The increased appreciation of the role of the immune system in cancer development and progression has led to new classes of therapeutics that specifically target mechanisms through which the tumour evades immune destruction."
They said that new drugs are already in clinical trials for other cancers, and encouraged testing these new drugs on "the novel immunogenic subtype of pancreatic cancer" they identified.
This study seems to have found important new information for researchers and doctors working on treatments for pancreatic cancer.
If doctors know the likely causal pathway of a particular tumour, they might be able to develop or choose a treatment known to work better for that pathway.
But there's a lot more work to do to prove the theory. This study is a starting point for new research to match particular treatments to particular classes of tumour.
Although the researchers suggest some treatments already being tested in other areas might now be successfully targeted at the immunogenic type of tumour, we don't yet know whether that will work. We need to see the results of clinical trials to test this idea.
In addition, it's unclear from the study whether there are new treatments that could be tested for all the subtypes of pancreatic cancer identified. We also don't know how feasible it is for everyone with pancreatic cancer to have their tumours genome sequenced before treatment.
So, while this study sounds like good news for the future treatment of pancreatic cancer, it may be a while before we know whether it's the breakthrough being hailed in the media.