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Can pancreatic cancer really be “wiped out” in less than a week? Not yet…

by Nick Peel | Analysis

7 January 2014

2 comments 2 comments

Microscope image of pancreatic cancer cells
Pancreatic cancer cells - image courtesy of the London Research Institute EM Unit

You may have seen reports in the news yesterday that Cancer Research UK scientists have uncovered a “treatment for one of the deadliest cancers” that can “wipe out the disease in less than a week”.

While we’re very pleased to see good-quality research being talked about in the media, it’s important to remember that this is still early stage laboratory work.

We don’t want cancer patients to take false hope from the headlines. Talk of a ‘cancer cure’ from this research is premature. But that’s not to say it isn’t exciting and potentially a crucial early step towards an effective new treatment.

To clear up the confusion and learn more about the work and next steps, we spoke to one of the scientists behind the research, Professor Doug Fearon, from our Cambridge Research Institute.

Early research in mice

While some newspapers (incorrectly) attribute liberal use of the word ‘cure’ to Professor Fearon, he is keen to stress that he was very clear that the work of his group has so far been within the confines of the laboratory, and it’s too early to claim any benefit in humans.

Researchers work with animal models that mirror human cancers as closely as possible to help make early discoveries about what might cause cancer and to trial new treatments before they are allowed to be tested in humans.

Professor Fearon’s lab worked with mice that develop pancreatic cancer that’s very similar to the human form of the disease.

He stressed that although the mouse model they used closely represents human pancreatic cancer, only time – and more research – will tell if this can be translated into patient benefit.

“Our next step is to take what we’ve learnt from the mouse models and test if the same processes are important in human pancreatic cancer”, he said.

So what did the research show? And what does this mean for pancreatic cancer patients in the future?

The immune system and cancer

The research marks another step forward in the field of immunotherapy – a compelling approach to harness the body’s own immune system and turn its focus towards cancer.

The immune system acts as our own personal ‘police force’.

But cancer cells can sometimes give the immune system the slip and some cells that interact with tumours can dampen the immune system and effectively shorten the ‘long arm of the law’.

Professor Fearon wanted to find out why immunotherapy has so far been ineffective in pancreatic cancer, and turned to mouse models to answer this crucial question.

An accurate model

Previous work from Professor Fearon’s lab showed that a particular type of cell linked to cancer, known as a carcinoma associated fibroblast – or CAF for short – was capable of suppressing the immune system.

Using a mouse model that accurately represents human pancreatic cancer, Professor Fearon’s team tested if the CAF cells play a role in how the immune system responds to pancreatic cancer.

They found that the model behaved a lot like the human form of the disease.

“Just as in people, the mice with pancreatic cancer didn’t respond to experimental immunotherapy treatments that have been showing huge promise in other types of cancer,” Professor Fearon said.

We’ve written about these promising treatments before – including an antibody drug that targets a molecule called PD-L1.

These drugs work by making the cancer cells ‘visible’ to the immune system again, allowing T-cells – the enforcement officers of the immune system – to attack and kill the cancer cells.

So just like in the human disease, the mice with pancreatic cancer didn’t respond to anti-PD-L1 immunotherapy. But why?

Professor Fearon’s work seems to have answered this crucial question, and – most importantly – found a way to make this treatment work in mice.

Breaking down a road block

“Although the tumours in the mice didn’t respond to the treatment, the mice did launch an immune response against the tumour, ” Professor Fearon said.

It turns out that the T-cells were facing a road block and were unable to reach the tumour.

“When we took a closer look at the tumours we could see that the T-cells were being excluded from the area around the tumour,” Professor Fearon added.

They were stopped in their tracks by a molecule that coated the cancer cells – called CXCL12 – and that molecule was being produced by the CAFs.

The team then used a drug – called AMD3100, or plerixaflor – that blocks an interaction between T-cells and the CXCL12 coating molecule.

This freed up the T-cells to target the tumour cells.

“When we combined the immunotherapy treatment with AMD3100 the cancer cells became sensitive to the immunotherapy treatment,” Professor Fearon said.

Combining these drugs was effective in shrinking the tumours that had previously not responded to treatment at all. And the response to treatment was encouragingly quick – within 6 days. But the disease wasn’t “eradicated within a week” as some papers reported.

Could this work in humans?

Professor Fearon pointed out that other research shows three key bits of evidence suggesting that human pancreatic cancer cells might be shielded from treatment in the same way.

  1. Human pancreatic cancer cells have the same molecular coating of CXCL12.
  2. CAFs are also present in human pancreatic cancer.
  3. T-cells are also excluded from pancreatic tumours in humans.

“We now want to test the drug combination in human pancreatic cancer patients to see if we see the same response,” Professor Fearon said.

Interestingly, those three key characteristics are also seen in bowel and ovarian cancers – not lung or ‘all’ cancers as some papers report – suggesting these cancer types may also respond to the drug combination.

What’s next?

The next step will be to test if the coating mechanism seen in the mouse models is also true in humans.

Professor Fearon believes this could have important implications for immunotherapy treatments.

“If the coating mechanism is shared across several tumour types then all types of immunotherapy that involve T-cells could potentially benefit from blocking the coating process,” he said.

Science most often progresses not in leaps and bounds, but in steady, small but significant steps. Professor Fearon and his team are working hard to take those important next steps, with the hope that more research will make yesterday’s misleading headlines the accurate ones of the future.

Nick

References

Feig C, et al. (2013). Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti-PD-L1 immunotherapy in pancreatic cancer, Proceedings of the National Academy of Sciences, 110 (50) 20212-20217. DOI:

Kraman M, et al. (2010). Suppression of Antitumor Immunity by Stromal Cells Expressing Fibroblast Activation Protein-alpha , Science, 330 (6005) 827-830. DOI:

    Comments

  • James Peters
    9 January 2014

    A study published in The American Journal of Cancer determined that cannabinoid receptors are expressed in human pancreatic tumor cell lines and tumour biopsies at much higher levels than in normal pancreatic tissue. Results showed that cannabinoid administration induced apoptosis. They also reduced the growth of tumour cells, and inhibited the spreading of pancreatic tumour cells. http://cancerres.aacrjournals.org/content/66/13/6748.abstract

  • Ronny Allan
    7 January 2014

    I am very interested in the detail and whether thw scientists include endocrine cancers that originate in the pancreas but are mostly classified as Neuroendocrine Cancers rather than Pancreatic Cancers (they are different in pathological, behavioural, treatment and in most cases prognostic terms). Or is this just the more common exocrine based pancreatic cancers being referred to?

  • reply
    Nick Peel
    8 January 2014

    Hi Ronny, thanks for your comment.
    The scientists used a mouse model that mirrors human pancreatic ductal adenocarcinoma (PDA), which is one of the more common exocrine forms of pancreatic cancer. They focussed on this particular form of pancreatic cancer as it is known that many patients with PDA do not respond to experimental immunotherapy treatments. More information about the different types of pancreatic cancer can be found here.
    Nick – Science Media Officer, Cancer Research UK

    Comments

  • James Peters
    9 January 2014

    A study published in The American Journal of Cancer determined that cannabinoid receptors are expressed in human pancreatic tumor cell lines and tumour biopsies at much higher levels than in normal pancreatic tissue. Results showed that cannabinoid administration induced apoptosis. They also reduced the growth of tumour cells, and inhibited the spreading of pancreatic tumour cells. http://cancerres.aacrjournals.org/content/66/13/6748.abstract

  • Ronny Allan
    7 January 2014

    I am very interested in the detail and whether thw scientists include endocrine cancers that originate in the pancreas but are mostly classified as Neuroendocrine Cancers rather than Pancreatic Cancers (they are different in pathological, behavioural, treatment and in most cases prognostic terms). Or is this just the more common exocrine based pancreatic cancers being referred to?

  • reply
    Nick Peel
    8 January 2014

    Hi Ronny, thanks for your comment.
    The scientists used a mouse model that mirrors human pancreatic ductal adenocarcinoma (PDA), which is one of the more common exocrine forms of pancreatic cancer. They focussed on this particular form of pancreatic cancer as it is known that many patients with PDA do not respond to experimental immunotherapy treatments. More information about the different types of pancreatic cancer can be found here.
    Nick – Science Media Officer, Cancer Research UK