Scientists discover two enzymes linked to pancreatic cancer – paving way to more precise treatment 

Scientists have discovered how the ratio of two enzymes could predict the chances of pancreatic cancer survival.

High levels of enzyme PHLPP1 and low levels of enzyme PKC in pancreatic tumors were linked to a poor prognosis, results of a new study found. But the reverse had better survival rates.

The team, from the University of California San Diego School of Medicine, says the findings could lead to using enzyme levels to predict pancreatic cancer prognosis.

They hope that it could lead to developing drugs that promote activity of the enzyme that curbs tumors and provide a potential treatment for sufferers of the disease like Jeopardy! host Alex Trebek.

 A new study from the University of California San Diego School of Medicine has found how the ratio of two enzymes could help predict pancreatic cancer survival and could even lead to treatment for sufferers like Alex Trebek (pictured, April 2017)

Pancreatic cancer is caused by the abnormal and uncontrolled growth of cells in the pancreas, a large gland in the digestive system.

It typically doesn’t show symptoms in the early stages. Sufferers tend to develop signs, such as back pain and jaundice, when it has spread to other organs.  

According to the American Cancer Society, around 56,000 will be diagnosed in the US in 2019, and around 45,000 will die from it.

Less than seven percent of patients survive five years, which means pancreatic cancer has one of the worst survival rates of all common cancers.

The new study builds on the team’s work in 2015 that found the enzyme PKC, which was believed to promote tumor growth, actually suppressed it.

‘It was thought to be an oncogene, something that caused cancer,’ first author Tim Baffi, a graduate student at UC San Diego School of Medicine, told DailyMail.com. 

‘Scientists had been trying to develop drugs that hindered PKC, but all those failed. So when it was revealed that PKC is a tumor suppressant, there was a big paradigm shift in the field.’ 

WHAT IS PANCREATIC CANCER? 

Pancreatic cancer is one of the most lethal forms of the disease. Around 95 percent of people who contract it die from it.  

Joan Crawford, Patrick Swayze and Luciano Pavarotti all died of pancreatic cancer. 

It is the fourth-leading killer in the United States. Around 10,000 people are diagnosed with pancreatic cancer each year in the UK, and 50,000 in the US.

WHAT IS THE CAUSE? 

It is caused by the abnormal and uncontrolled growth of cells in the pancreas – a large gland in the digestive system.

WHO HAS THE HIGHEST RISK?

Most cases (90 percent) are in people over the age of 55. Around half of all new cases occur in people aged 75 or older. One in 10 cases are attributed to genetics.

Other causes include age, smoking and other health conditions, including diabetes. About 80 percent of pancreatic cancer patients have some form of diabetes. 

WHY IS IT SO LETHAL?

There is no screening method for pancreatic cancer. Pancreatic cancer typically does not show symptoms in the early stages, when it would be more manageable. 

Sufferers tend to start developing the tell-tale signs – jaundice and abdominal pain – around stage 3 or 4, when it has likely already spread to other organs. 

WHAT ARE THE SURVIVAL RATES? 

For all stages of pancreatic cancer combined, the one-year survival rate is 20 percent. At five years, that rate falls to just nine percent. 

If the cancer is caught in stage 1A, the five year survival rates is about 14 percent and 12 percent for 1B. 

At stage 2, those rates are seven and five percent, respectively. For a pancreatic cancer in its third stage, only three percent of people will survive another five years. 

By stage IV, the five-year survival rate falls to just one percent.  

WHAT ARE THE TREATMENT OPTIONS? 

The only effective treatment is removal of the pancreas. This proves largely ineffective for those whose cancer has spread to other organs. In those cases, palliative care is advised to ease their pain at the end of their life.  

 

Baffi said the lab at UC San Diego School of Medicine had discovered another enzyme called PHLPP1 in 2005.

This enzyme, they discovered, regulates the one that curbs tumor growth.

When the tumor suppressing switch is turned ‘on’, the other enzyme ‘tags’ it and make sure it’s destroyed. 

‘This means the more PHLPP1 you have, the less PKC you have,’ Baffi said. 

For the study, published in the journal Molecular Cell, the team looked at 105 pancreatic cancer tumors to analyze the enzyme levels in each one.

About 50 percent of patients lived longer than five-and-a-half years. 

They found that patients with poor survival rates had high levels of the regulating enzyme and low levels of the tumor-suppressing enzyme.  

Conversely, those with better outcomes had low levels of regulating enzyme and high levels of the tumor-suppressing one, which led to much better outcomes.  

Knowing this distinction, Baffi says, is a significant step in the fight to crack this notoriously elusive type of cancer.

In theory, drug compounds could promote activity of the tumor-suppressing enzyme to shift the ratio in patients with poorer odds.

That is what Baffi’s team is investigating next.

‘This has important implications especially for pancreatic cancer therapy,’ he said.

‘The first is that it could be able to predict cancer prognosis – whether it’s good or not – and, second, it might also lead to an avenue for targeting cancer with drug therapies. 

‘Trying to understand the biochemistry behind cancer, what’s going on behind these diseases, could lead to treatment.’ 

The notoriously hard-to-treat disease came to the forefront of the news earlier this month when Alex Trebek, the 78-year-old longtime host of Jeopardy, revealed he had stage 4 pancreatic cancer.

In a video posted on the game show’s YouTube page, he revealed that the prognosis was ‘not very encouraging’.

‘I…wanted to prevent you from reading or hearing some overblown or inaccurate reports regarding my health,’ he told fans.

‘Now normally, the prognosis for this is not very encouraging, but I’m going to fight this, and I’m going to keep working.

‘And with the love and support of my family and friends and with the help of your prayers also, I plan to beat the low survival rate statistics for this disease.

‘Truth told, I have to! Because under the terms of my contract, I have to host Jeopardy! for three more years!

‘So help me. Keep the faith and we’ll win. We’ll get it done. Thank you.’

Read more at DailyMail.co.uk