Every two minutes, someone in the UK is diagnosed with cancer. In 2016, 784 new cases of pancreatic cancer were diagnosed in Scotland alone, according to Pancreatic Cancer UK (PCUK). Furthermore, the majority of cases (~80%) are diagnosed at late stage disease and unfortunately 44% of cases are diagnosed following emergency admission to hospital (PCUK).
Throughout our lives, our cells are continuously dividing to allow us to grow, replace old/damaged cells, and repair tissues following injury. However, during division, cells have to copy their DNA which may lead to errors, known as mutations, that promote abnormal growth giving rise to a neoplasm (new growth) or tumour mass. This may be benign which is commonly referred to as “non-cancerous”. Otherwise, tumours can be malignant, which is when cells continue to divide and spread to other parts of the body (metastases). This is what we refer to as “cancer” and may arise from any of the 37.2 trillion cells that make up the human body.
It is vital to remember that cancer is not one disease and that no two individuals with the same cancer type are identical. With November being Pancreatic Cancer Awareness month, I wanted to share some insight into the unique challenges of this disease and to highlight the symptoms of the 11th most common cancer worldwide.
Here are a few solemn facts… that you really need to be aware of.
Pancreatic cancer is currently the 3rd and 5th leading cause of cancer related death in the US and UK respectively and is predicted to overtake lung cancer (US) and breast cancer (UK) deaths as early as 2025. In Scotland alone, the incidence of pancreatic cancer was found to have increased by 12% between 2007-2017 (BBC) and therefore it is vital that research continues to search for novel methods of early detection and that funding remains available for development of new medicines.
Despite substantial advances in molecular biology technologies and development of immunotherapies, Cancer Research UK has described pancreatic cancer as one of the ‘cancers of unmet need’. Surgical resection remains the only ‘curative’ treatment and is only advised in 10% cases due to the presence of metastases at diagnosis. Pancreatic cancer metastases often refers to the presence of pancreatic tumour cells in the lymph nodes, liver or lungs. Nevertheless, when surgery is performed, it remains difficult for doctors to monitor the return of disease in follow-up appointments. The returning of disease is referred to as relapse and often presents further complications, with the major one being increased drug resistance.
With that said, the pancreas is a fascinating organ. Here’s why.
Like any other organ, the pancreas is made up of several cell types. However, the pancreas is unique in that it has a vital role in two contrasting physiological systems: the digestion of our food (exocrine) and the production of hormones (endocrine).
The most common form of pancreatic cancer is pancreatic adenocarcinoma (PDAC) (85% cases) which develops from epithelial cells of the pancreas. Less commonly, pancreatic neuroendocrine tumours (PNETs), which constitute approx. 7% cases, may occur. These tumours develop from the islet cells of pancreas, which produce hormones such as insulin and glucagon. Rarely, pancreatic tumours may arise from acinar cells that produces digestive enzymes.
The location and size of the pancreas means that non-invasive methods for screening or diagnosis remains a challenge in the field, however current research hopes to develop an accurate screening method which would most likely be offered to high-risk patients (i.e. those with familial history) in the first instance.
There are several risk factors for pancreatic cancer including:
- Smoking (accounts for 30% cases)
- Obesity (may account for the increasing incidence)
- Family history (10% cases)
- Diabetes (mellitus) – an autoimmune disease in which the body’s immune system attacks the islet cells leading to deregulation of sugar levels in the bloodstream
- Chronic pancreatitis – prolonged inflammation of pancreatic tissue which may occur as a result of smoking/alcohol consumption and familial history
The biology can be overwhelming, but here’s what you need to look out for.
One of the dominating challenges in pancreatic cancer is that it is a largely asymptomatic disease meaning that clinical symptoms are only apparent at late stages of disease. The key symptoms of pancreatic cancer are rarely specific to this disease, but it is so important to prioritise a visit to your GP if you, or a loved one, show any of these symptoms.
- Jaundice – this refers to colouring, or yellowing, of the skin and eye white and is caused by blockage of the bile duct which drains the liver. This blockage leads to build up of a waste substance, or metabolite, known as bilirubin, which pigments, or changes the colour, of the skin and causes itch.
- Severe abdominal pain that may be felt from the back
- Weight-loss – pancreatic cancer most often occurs at the head of the pancreas and can obstruct the pancreatic duct. This may prevent digestive enzymes from entering the digestive system, preventing absorption of nutrients through the walls of the intestine following breakdown.
- New-onset diabetes – this refers to acute development of diabetes, which otherwise has no suspected cause and is a red flag symptom when it occurs in a patient >50yrs of age. Symptoms of diabetes include extreme thirst, regular urination, fatigue, compromised vision, and irritable behaviour.
That’s a wholesome clinical perspective… but, what about ongoing research?
One of the biggest challenges in cancer research is identification of suitable, sensitive biomarkers for early detection of disease. Pancreatic cancer is no exception, particularly as metastases occurs in early stages, preventing surgical resection in the majority of cases. Additionally, research aims further characterise the molecular subtypes of PDAC and uncover mechanisms of drug resistance to enable the development of new drugs or treatment combinations that will improve clinical management of disease.
As with many cancer types, it is unlikely that researchers will find one drug that can treat pancreatic cancer when administered alone. Recent studies have led to the combination therapy, known as FOLFIRINOX becoming the standard of care for fit patients with advanced metastatic pancreatic cancer, however the improvement of disease state remains suboptimal. Another chemotherapy in clinic is known as Abraxane™ which is a modified version of the traditional chemotherapy, Gemcitabine. Unlike other in cancers, such as melanoma, novel therapies targeting the immune system, known as immunotherapies, have shown little promise in pancreatic cancer to date. Nevertheless, ongoing research hopes to overcome the limitations of such therapies.
Key research, led by the team in Glasgow, aims to identify subgroups of patients that are, for one reason or another, more responsive to a defined therapeutic option. Our team aims to perform genetic profiling and interrogate the immune landscape pre- and post- chemotherapy and/or surgery. It is vital that we develop a clinical test that can categorically determine which drug treatment is best for each individual patient which would be administered at the ‘right time’ to improve overall survival. This concept is referred to as precision medicine and is likely to be the foundation of cancer therapy in years to come.