Progress in pancreatic cancer

Pancreatic cancer cells (credit: LRI EM Unit)

Pancreatic cancer comes with stark statistics attached. Often not diagnosed until it has spread, it’s one of the most difficult types of cancer to treat. Fewer than one in five patients (16 per cent) survive for more than a year after diagnosis.

The good news is that progress is being made – survival rates have increased since the 1970s, when only half as many patients survived this long. But it’s easy to see that there’s still a lot of room for improvement.

Cancer Research UK scientists are helping to bring these much-needed improvements to patients, and we’re investing in pancreatic cancer research as part of our five-year research strategy.

A recent study into a new approach to treatment and a new clinical trial testing an experimental drug both highlight the science behind our search for better treatments for pancreatic cancer.

Src – a key player in pancreatic cancer?

In a study published in the journal Gastroenterology in July, a group of our researchers in Scotland investigated the role of a ‘messenger’ protein called Src (pronounced ‘sark’) in pancreatic cancer.

Src helps to transmit signals inside cells that tell them to divide. Previous studies have shown that Src is overactive in several types of cancer, including pancreatic, breast and bowel cancer. It’s likely that this overactive signalling encourages the cancer cells to grow out of control and spread around the body. The evidence so far  suggests that understanding Src could give important clues for new ways to treat some types of cancer.

To find out more about Src’s role in pancreatic cancer, the researchers looked at levels of the protein in samples from 114 tumours. The large majority (over 70 per cent) had higher levels of Src than healthy pancreatic tissue from the same patient.

Importantly, the more advanced the tumour, the higher its levels of Src tended to be. And patients whose tumours had lower levels of Src tended to survive longer after surgery compared to patients whose cancers had more Src.

‘Modelling’ pancreatic cancer

The next step was to look at Src in a living organism. To do this the researchers worked with a mouse ‘model’ of pancreatic cancer.

The ‘model’ allows researchers to study a disease that is extremely similar to pancreatic cancer in humans. It’s used to help develop new approaches for  treatment, allowing researchers to predict if drugs will be safe and effective.

Tests on pancreatic tissue showed that signals from Src became more active as the tissue changed from being healthy to becoming cancerous. These results, along with those from human tumours, suggest that the increase in Src activity is linked to the progression of the cancer.

Interrupting Src signalling

The researchers then investigated whether interrupting Src signalling inside the cells could slow the cancer’s growth. Several drugs that affect Src are being developed and tested, and in this case the researchers chose one called dasatinib, which is already used to treat some types of leukaemia.

Using pancreatic cancer cells growing in the lab, the researchers found that dasatinib interfered with Src signalling, and so slowed the cancer cells’ movement.

This discovery raises a fascinating question – if cancer cells can’t move, they can’t spread, so could this drug prevent pancreatic cancer from spreading around the body?

It’s one thing to put the brakes on cancer cells in the lab, but more tests were needed to see if dasatinib had the same effect in ‘real life’. To find out, the researchers compared two groups of mice with pancreatic cancer – one group was treated with dasatinib, while the other was not.

Although the treated group didn’t live any longer than those that weren’t treated, the team found that their cancers had spread much less. Only about a quarter (23 per cent) of the treated group had tumours in other parts of the body, compared to nearly two thirds (61 per cent) of the untreated group.

The next step

According to the researchers, it seems that while dasatinib doesn’t stop the main tumour in the pancreas from growing, it does prevent cancer cells from spreading to other organs. They suggest that this drug could be of real benefit to people with pancreatic cancer – those who are able to have surgery to remove the main tumour could be treated with dasatinib to reduce the risk of the cancer spreading.

The next step is to test the drug further, with the aim of starting clinical trials in patients if the results are encouraging. But this work has already given us important clues to whether the drug could help humans with the disease, speeding up progress that is so urgently needed.

A new clinical trial

In a separate development, this month Cancer Research UK’s Drug Development Office has launched a new trial to test a different experimental drug for pancreatic cancer, the snappily-named MK-0752. The drug works by blocking enzymes needed to fuel the growth of pancreatic cancer cells. It blocks a particular signalling pathway called Notch, causing the cancer cells to self-destruct.

The drug will be given to patients with advanced pancreatic cancer in combination with the standard treatment, a chemotherapy drug called gemcitabine. The first stage of the trial will test the safety of MK-0752 and help to find the best dose. The next step is to test how effective it is against pancreatic cancer.

There are very few treatments for pancreatic cancer, especially when it’s advanced. Clinical trials like this one are a key part of efforts to find new ways to tackle the disease.

Making progress

These two studies highlight the challenge of research into pancreatic cancer, and the hard work that’s required to make progress. Every cancer presents unique challenges, and pancreatic cancer is a particularly difficult problem.

Research like this adds vital knowledge to our understanding of the disease – the best weapon we have in the fight against cancer.

Nell Barrie

References

Morton JP, Karim SA, Graham K, Timpson P, Jamieson N, Athineos D, Doyle B, McKay C, Heung MY, Oien KA, Frame MC, Evans TR, Sansom OJ, & Brunton VG (2010). Dasatinib inhibits the development of metastases in a mouse model of pancreatic ductal adenocarcinoma. Gastroenterology, 139 (1), 292-303 PMID: 20303350

Frame MC (2002). Src in cancer: deregulation and consequences for cell behaviour. Biochimica et biophysica acta, 1602 (2), 114-30 PMID: 12020799

Brunton VG, & Frame MC (2008). Src and focal adhesion kinase as therapeutic targets in cancer. Current opinion in pharmacology, 8 (4), 427-32 PMID: 18625340