Pancreatic cancer may lurk in the body for many years before patients fall ill, US scientists say
Research hints at earlier opportunities to spot and treat the disease, which is fatal in 95% of cases.
Genetic analysis of tumours by the Howard Hughes Medical Institute and Johns Hopkins University suggested the first mutations may happen 20 years before they become lethal.
UK survival rates for the disease have not improved in the past 40 years.
The disease is often aggressive and unresponsive to treatment by the time it is diagnosed.
The study, published by the Nature journal, found that tumours appear to be slow growing.
Pancreatic cancer
Pancreatic cancer is among the most lethal malignancies, with fewer than 5% of patients still alive five years after diagnosis.
It has long been suspected the disease is so deadly because it grows so quickly, but surprising new research finds the opposite to be true.
The investigation found that pancreatic cancer develops and spreads much more slowly than has been thought, with the timeline from when it first forms to when it kills spanning two decades or more, says Christine Iacobuzio-Donahue, MD, PhD, of Baltimore’s Johns Hopkins Sol Goldman Pancreatic Cancer Research Center.
That means effective early detection strategies could have a major impact on outcomes, transforming a highly fatal disease into a largely treatable or sometimes preventable one like colon cancer, she adds.
The research appears in the Oct. 28 issue of the journal Nature.
In its early stages, cancer of the pancreas — the gland that aids digestion and helps control blood sugar levels — causes vague symptoms or none at all. That’s why people are typically diagnosed after the cancer has spread beyond the pancreas, and why the disease is often fatal. This year, pancreatic cancer will cause about 36,800 deaths, according to the U.S. National Cancer Institute.
Pancreatic cancer
Because people with pancreatic cancer typically die within a year of diagnosis, it may seem as if this form of cancer progresses rapidly, said Iacobuzio-Donahue.
“But what we’ve learned is that it is actually a long, slow process, and metastasis happens at the very end, within the final two to three years. Before that time, there is a tremendous window of opportunity for screening,” she said. “We just have to modify our screening methods to better diagnose people at an earlier time point.”
In the future, new imaging techniques and blood tests will offer hope for early detection, the study noted. And just as people have a colonoscopy when they turn 50, “perhaps they should have an endoscopy of their upper gastrointestinal organs that includes an ultrasound of the pancreas,” said Iacobuzio-Donahue. Screenings for colon and breast cancers are based on age and health history, rather than symptoms, she noted. “But we screen people for pancreatic cancer based on how they feel,” she said. “And by the time they feel sick, it’s too late.”
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Johns Hopkins scientists have made a new discovery that could be helpful in the fight against pancreatic cancer.
By determining what goes missing in human cells when the gene that is most commonly mutated in pancreatic cancer gets turned on, scientists have discovered a potential strategy for therapy.
The production of a particular cluster of genetic snippets known as microRNAs is dramatically reduced in human pancreatic tumor cells compared to healthy tissue, according to the study.
When the team restored this tiny regulator, called miR-143/145, back to normal levels in human pancreatic cancer cells, those cells lost their ability to form tumors.
The team focused its investigation on KRAS, a member of the important RAS family of oncogenes that is mutated in almost all cases of the most common form of pancreatic cancer.
The researchers conducted their studies in a multitude of model systems — human cells growing in culture as well as those harvested directly from tumors, and also in mice and zebrafish.
First, using cell lines derived from pancreatic tumors and growing in culture, they added gene products such as mutant KRAS and an inhibitor of mutant KRAS, and then measured the microRNA responses.
Next, they conducted the same experiments using cells from patients” pancreatic tumors. Finally, they looked at pancreatic tissue from mice and zebrafish to see what happened when KRAS was activated.
Every time, the team noted the same robust findings. When KRAS was activated, the microRNA cluster miR-143/145 was powerfully repressed, to a fraction of the levels in normal, non-cancerous cells.
Restoring the expression of miR-143/145 back to the level of normal cells was sufficient to confer “a very striking change in behavior of those cells,” said Josh Mendell from Johns Hopkins University School of Medicine.
The study has been published in Genes and Development, Dec. 15.
Nearly one in four cancer patients in England is diagnosed only when they arrive at hospital in an emergency, a national study suggests.
The National Cancer Intelligence Network (NCIN), which looked at data from diagnoses in 2007, found 23% of cases had been detected at that stage.
In the cases of acute leukaemia and brain cancer, half of cases were only discovered at a critical stage.
Cancer Research UK said more education was needed to recognise symptoms.
The NCIN report suggested those who were diagnosed only at the emergency stage were more likely to die within a year than those diagnosed earlier.
Harpal Kumar, the chief executive of Cancer Research UK, told the Daily Telegraph: “The figure for diagnoses via emergency presentations is way too high.
“This statistic helps explain why we have lower survival rates than we would hope to have, lower than the best countries in Europe.
“We need screening programmes to be rolled out as early as possible and GPs given rapid access to the tests that will enable patients to be moved quickly through the system.”
The survey suggested those on low incomes, elderly people and the under-25s were the most likely to be diagnosed at a late stage.
Only 3% of skin cancers went undetected until the emergency stage, compared with 58% of brain cancers.
Sara Hiom, director of health information at Cancer Research UK, said the late diagnosis levels were “alarmingly high”.
She said: “We hope the government will seriously consider the best way to tackle this problem in their revised cancer strategy, which is due in the coming months.”
Gemma Larkin from Cambridge, was diagnosed with a brain tumour and agrees regular scanning would help detection.
She told the BBC: “For a year prior to the diagnosis I had been fobbed off with a diagnosis of stress headache and then early diabetes. It wasn’t until I lost the sight in my left eye and was sent for MRI and CT scans that doctors realised my symptoms were a brain tumour.
“Now – 18 months, three surgeries and radiation therapy later – I am still struggling through chemotherapy hoping that this will be the treatment which cures me.”
However, the 28-year-old does not blame her GP.
“Brain tumours at my age are rare, so I don’t bear a grudge toward my doctors, but regular scanning could reduce the number of cancer related deaths so easily. This would also reduce the pressure on GPs to diagnose with limited facilities available to them.”
A spokesman for the Department of Health said: “We are committed to improving cancer outcomes. Earlier diagnosis is crucial to match the best survival rates in Europe.”
Last December, government cancer tsar Professor Mike Richards said the NHS in England needed to get better at diagnosing cancers at an earlier stage if it was to continue to improve survival rates.
He called for a greater focus on one-year survival rates, an indication that cancer was spotted at a treatable stage.
“Lethal pancreatic cancer grows for decades,” according to the BBC. The cancer may “lurk in the body for many years before patients fall ill”, it said.
The news is based on a study that has estimated the way pancreatic cancer progresses by examining tumours taken from seven patients killed by the disease. By examining the genetics of these tumours, scientists calculated that the first cancer-related mutations in pancreatic cells take place on average 18 years before the cancer is able to spread to other organs. It takes about 20 years before patients die from the disease.
This laboratory study has used genetic sequencing and a mathematical model to estimate the patterns of progression for pancreatic cancer, a disease that often goes undetected until it reaches an incurable stage. While its conclusions would need to be confirmed in further studies, they suggest that there could be a large window of opportunity to detect and treat the cancer before it spreads and becomes lethal. As things stand, only 2-3% of people with advanced pancreatic cancer are alive five years after their first diagnosis, and research in this area is of great importance.