Pancreatic cancer is among the hardest cancers to treat. NYU Langone says the most common form kills nearly 85% of patients within five years of diagnosis. A new study in the journal Nature Genetics points to one reason: inside a single tumour, the cells are not all alike, and they can shift between a milder state and a more aggressive one.
It is a study of tumour samples and lab experiments. It does not show a new treatment working in patients.
What the study found
The researchers, from NYU Langone Health with colleagues at Oregon Health and Science University and the University of California San Diego, published the work online on 13 October. The lead author is Despoina Kalfakakou, and the senior authors are Aristotelis Tsirigos and Diane Simeone. They looked at gene activity in 443,451 individual cells from 62 tumours taken from 56 people with pancreatic ductal adenocarcinoma, the most common form of the disease.
Six of the patients gave samples both before and after chemotherapy, which let the team compare the same person’s tumour at two points.
Cells that switch state
Earlier work sorted this cancer into two broad types. The classical type is less aggressive, and the basal type is more aggressive. What those studies could not explain was how cells move between the two.
The new data suggest that it happens through clones, which are groups of cancer cells that share the same genetic changes. On average, each tumour held between two and 11 clones of basal and classical cells. Some clones evolved to resist treatment. Others gained the ability to spread quickly. The authors link the genetic reshuffling inside a tumour to those shifts.
One caution from the release: the relationships between clones were inferred from gene activity, not measured directly.
Two genes in the spotlight
| Gene | What the team saw | How firm it is |
|---|---|---|
| MYC | More active in the aggressive cell populations | Seen in the samples |
| TIGIT | More active in some clones, where it helps cancer cells avoid the immune system | Seen in the samples |
| PD-1 | Less active in those same cells | Authors say it may explain why PD-1 immunotherapies rarely work here |
What is still lab work
In experiments, blocking MYC in basal cells pushed them back towards the less aggressive classical state and made them more exposed to immune cells. The release does not say which laboratory model was used, and the effect has not been shown in patients.
Dr Tsirigos says trials of MYC and TIGIT inhibitors, in pancreatic and other cancers, are under way. This study does not show that those drugs work against pancreatic cancer. The paired before-and-after samples also come from only six people, so the chemotherapy findings rest on a small group.
The work was funded by the US National Institutes of Health and the Sky Foundation.
What it means
Our reading: the study gives researchers a more detailed map of why one tumour can contain cells that respond differently to the same treatment. That is a reason to study treatments aimed at the cell state, not only at the average tumour. It is not advice for patients, and anyone affected by pancreatic cancer should talk to their care team about options.
For another recent health study that finds a link but cannot prove cause, see a seven-year Parkinson’s study that finds a link but cannot prove cause.
What we could not confirm
We did not open the paper in Nature Genetics, so the numbers come from NYU Langone’s release. We could not check which model the MYC experiments used or how many cells came from each patient. We have not found reactions from researchers outside the team.
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