Cancer - Pancreatic
The Garvan is striving to improve the diagnosis, prognosis and treatments for patients with pancreatic cancer. If you would like more information on pancreatic cancer, or learn more about Garvan's work, click through the links below.
Pancreatic cancer is the fourth leading cause of cancer death in men and women in Western societies.
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The pancreas is an organ of the digestive system. The pancreas is a small eggplant-shaped gland about 18-25 cm long that is located behind the stomach and sits close to the duodenum.
The pancreas functions as an exocrine and endocrine organ:
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The endocrine cells of the pancreas – the Islets of Langerhans – are responsible for the production and secretion of many important hormones in the bloodstream. The main pancreatic hormones, insulin and glucagon, regulate blood sugar levels in the blood.
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The exocrine cells of the pancreas – the acinar cells – secrete pancreatic juice into the duodenum. Pancreatic juice contains digestive enzymes that help digest food, particularly protein.
Some of the disorders of the pancreas include:
Chronic pancreatitisDiabetesPancreatic cancer (for further information on pancreatic cancer click through the links below).
Pancreatic cancer is an abnormal uncontrolled growth of cells in the pancreas. The most common subtype of pancreatic cancer begins in the pancreatic ducts and spreads into the body of the pancreas. The surrounding nerves and blood vessels may also be infiltrated with cancerous cells.
The cancer can spread to other organs of the body via the blood and lymphatics.
Pancreatic cancer is often referred to as a ‘silent disease’ because it is frequently diagnosed in the later stages of growth. This can occur because the pancreas is located behind the stomach and the cancer can remain undetected until it grows large enough to affect nearby organs.
Treatments and survival rates for pancreatic cancer have not changed for almost 50 years1.
Prognosis is poor for patients with advanced pancreatic cancer.
Little is known about the causes of pancreatic cancer however there are some factors that can increase your risk of developing the disease:
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Age: 80% of cases are diagnosed in people over 60. Pancreatic cancer is uncommon in people under 40
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Smoking: doubles your risk
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Chronic pancreatitis: long-term inflammation of the pancreas can increase your risk 5-fold
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Diabetes: the long-standing association between pancreatic cancer and diabetes is not well understood. It is possible that the cancer causes some cases of diabetes, rather than the diabetes causing the cancer
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Genetics: there may be a genetic link in up to 1 in 10 cases of pancreatic cancer. A number of gene mutations can increase your risk -
Breast cancer gene 2 (BRCA2)
Peutz-Jeghers Syndrome
Familial Atypical Mole Melanoma (FAMM)
Hereditary Non-Polyposis Colorectal Cancer (HNPCC)
Familial Adenomatous Polyposis (FAP)
Individuals with a strong family history of pancreatic cancer have an increased risk of developing the disease themselves.
Pancreatic cancer is a disease of inherited and acquired gene mutations. These genes are involved in cell cycle regulation, cell survival and invasion of cancer cells to other sites. Some of these genes include:
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Wnt – the Wnt signaling pathway may act as a determinant of tumour fate within the pancreas
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p53 - has many biological functions, including the regulation of programmed cell death and inhibition of cell growth following DNA damage. Mutations in p53 occur in approximately 50% of all cancers and the ‘switching-off’ of p53 has been reported in up to 75% of pancreatic cancers
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Cyclin D1 – increased expression of this gene is found in up to 68% of pancreatic cancers and is a marker of poor outcome
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HDAC2 – increased expression of this gene is found in advanced pancreatic cancers
The cause of pancreatic cancer remains elusive.
The most consistently identified risk factor is cigarette smoking. Genetic factors are known to play a role in less than 10% of the total pancreatic cancers.
The cell that first initiates pancreatic cancer is unknown. However populations of cells have been identified that may be responsible for tumour initiation, invasion of the cancerous cells to other parts of the body and resistance to current therapies.
Three distinct precursor lesions to pancreatic cancer have been identified:
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pancreatic intraepithelial neoplasia (PanIN)
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intraductal papillary mucinous neoplasm (IPMN)
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mucinous cystic neoplasm (MCN).
If these non-invasive lesions can be detected and treated before they progress to an invasive cancer, the outcome for patients will improve.
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Abdominal pain: usually occurs in the upper abdomen and can radiate to the back. Pain can worsen when lying down or after eating
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Weight loss: weight loss is common in patients with pancreatic cancer and is usually one of the first symptoms
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Yellowish skin and eyes, and dark urine: Jaundice, a condition marked by yellowing of the skin or eyes, occurs when the tumour blocks the bile duct
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Nausea and vomiting: a common symptom that can delay diagnosis because the symptom is not specific to pancreatic cancer
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Loss of appetite: another non-specific symptom of pancreatic cancer
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Itchy skin: a less common symptom of pancreatic cancer
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Unexpected onset of diabetes: the pancreatic tumour can prevent the pancreas from producing insulin
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Change in bowel motions: either diarrhoea or severe constipation
Pancreatic cancer is the 4th most common cause of death from cancer in Australia and over 2000 new cases are diagnosed each year1. By the age of 75 years, 1 in 117 males and 1 in 188 females will be diagnosed with pancreatic cancer in NSW2.
In NSW, approximately only 7% of patients survive 5 years following diagnosis2.
The incidence of pancreatic cancer is increasing.
Unfortunately, most cases of pancreatic cancer may not have been preventable.
The best way to prevent pancreatic cancer is to avoid the risk factors. One of the most avoidable risk factors is smoking. A balanced diet and regular exercise also play a part in preventing cancer.
Treatment options differ from patient to patient, and are based on several factors, including:
A combination of therapies can be used to prevent the tumour from spreading, to relieve symptoms and to maintain a better quality of life:
Surgery
- Operations to remove tumours are the primary treatment option for patients with pancreatic cancer. However, only 20% of patients present with a tumour that is localised to the pancreas and has not spread to other organs
- the most common surgical procedure is referred to as the ‘Whipple Procedure’. In this procedure, the head of the pancreas is removed, along with some of the duodenum, gall bladder and bile duct. Enough of the pancreas is left to maintain some function
- surgery can also involve removal of the head and tail of the pancreas, or complete removal of the pancreas
Unfortunately surgery is not always a cure. Only 10–20% of patients who undergo surgery to remove all or part of their pancreas survive for more than 3 years following surgery.
At present, there are no molecular markers that indicate outcome following surgery. One gene that is currently being studied is LMO4. Low or no LMO4 expression may indicate a poor outcome following surgery while high LMO4 expression can be associated with a significant survival advantage following surgery. This marker is currently being validated for future use in the treatment of pancreatic cancer.
Endoscopic treatment
- if the tumour is blocking the bile duct, a stent may be inserted in the bile duct to allow bile to drain from the liver
Radiation therapy
- uses high-energy x-rays which shrink or destroy tumour cells, the most common form is external beam radiation therapy
- may be used to treat locally advanced pancreatic cancer that cannot be removed with surgery
- may also be used to relieve symptoms
Chemotherapy
- involves the use of anti-cancer drugs to prevent the cancer cells from dividing
- is sometimes used in combination with radiation therapy
Biological therapies
- there is increasing use of targeted treatments such as monoclonal antibodies and small molecules that can block growth factors on cancer cells
Established in 2008, the International Cancer Genome Consortium (ICGC) brings together leading cancer researchers across the world, through 11 funding organisations in 12 countries, and aims to catalogue the genetic changes of the 50 most common cancers. The Garvan is making a substantial contribution to the ICGC by tackling pancreatic cancer.
The Australian Pancreatic Cancer Genome Initiative (APGI) is the Australian arm of the international consortium. Together with collaborators from the Institute of Molecular Biosciences in Brisbane, and other specialists, Garvan researchers are looking to examine genes from 400 pancreatic tumour samples with the aim of determining the exact genetic aberrations in each tumour. This information will help us to determine why some drug treatments work and why others do not, and will help researchers to design new drug therapies to specifically target the genetic aberrations in each tumour.
The information from this study, and in all of the ICGC projects, will be made freely available on the internet and will help the development of new diagnostic tools and targeted therapies for pancreatic cancer patients.
News
Helping pancreatic cancer surgeons make tiebreaker decisions
MEDIA RELEASE:
15 Apr 2011
Garvan researchers have identified two ‘biomarkers’ that appear to have the ability to predict patient survival after surgery for pancreatic cancer before the operation takes place. It is the first predictive tool of its kind for this most deadly of cancers. The American Society of Clinical Oncology (ASCO) highlights the finding in its current newsletter (ASCO Post) – distributed globally to a broad audience of cancer professionals.
$3.7 million to push cancer discoveries down the ‘pipeline’
14 Oct 2010
The Cancer Institute NSW has awarded the Garvan Institute’s Cancer Research Program $3.7 million, research funding that should lead to improved clinical decision-making for breast, prostate and pancreatic cancer within the next 5 years.
