Combatting the elusiveness of pancreatic cancer

Early detection methods remain evasive

Pancreatic cancer entered the limelight recently when the co-founder and CEO of Apple Steve Jobs was diagnosed with the disease. Shortly after receiving the diagnosis, Jobs gave a commencement speech in 2005 at Stanford University where he said, “Your time is limited, so don’t waste it living someone else’s life.” These words came from a man who had seemingly realized that his time on this earth was soon coming to an end. Pancreatic cancer is notoriously difficult to diagnose. The issue of recognizing and diagnosing pancreatic cancer has been brushed aside for far too long, and it’s time that we paid more attention to it.

A deadly disease

Pancreatic cancer is unique fom other cancers in that its close anatomical association to many vital blood vessels bolsters its ability to spread to other organs. Because of this, pancreatic cancer is the fourth leading cause of cancer associated death in Canada.

The pancreas is an organ located behind the stomach which is responsible for producing vital hormones such as insulin as well as pancreatic polypeptide. Although humans can live without a pancreas, this comes with consequences. The pancreas aids in the absorption and digestion of nutrients by secreting digestive enzymes. There is a rising incidence of pancreatic cancer worldwide, and based on a 2009 estimate, pancreatic cancer is projected to be the second leading cause of cancer-related death in the U.S by 2030 surpassing breast and prostate cancer. Perhaps most alarming is that pancreatic cancer is responsible for the highest rate of cancerassociated mortality and – despite our efforts in cancer treatments – the overall survival rate of patients with pancreatic cancer has remained essentially unchanged over the past four decades.

Pancreatic cancer is very difficult to detect as in its early stages patients often remain asymptomatic for a long time. Symptoms that do manifest often do so in the form of very non-specific symptoms such as back pain, changes in stool, jaundice, or loss of appetite; these can easily be mistaken for other relatively minor health issues. Because of this, when a patient is diagnosed with pancreatic cancer, it is usually already at an advanced stage. This is mainly because, as the American Cancer Society notes, there is still no reliable method for early detection.

In the U.S., more than 60 per cent of all cancers affect those over the age of 65, and pancreatic cancer is no exception. The average age for a patient diagnosed with pancreatic cancer is approximately 70. A paltry 8 per cent of those diagnosed live more than five years post- diagnosis. According to the Hirshberg Foundation for Pancreatic Cancer Research, if someone is diagnosed with metastatic pancreatic cancer (meaning, one that is confirmed to have potential to spread to other parts of the body), the average life expectancy is less than six months.

To make matters worse, in about 80 per cent of pancreatic cancers, the tumours are at such late stages that surgery is not a viable option. In these cases, clinicians have to rely on other methods of treatment such as radiation and chemotherapy. Despite its deadliness, there is a lack of media attention given to pancreatic cancer, with other diseases such as breast cancer often receiving much more consistent popular media attention, The U.S. National Cancer Institute calculated in 2011 that research and fundraising for breast cancer raised 15,638 USD per death, while pancreatic cancer only received 2,641 USD per death.

The search for a cure

It is difficult to know where to start researching when trying to address such a deadly and complex disease. The common approach is to focus on a particular pathway or marker for a disease. Rather than follow this approach, however a Johns Hopkins research team led by Victor Velculescu chose to look for de novo (newly acquired) mutations in an attempt for an unbiased analysis of the entire genome of the patient, instead of looking at known mutations relating to pancreatic cancer. This involved looking at 24 tumours, as well as the analysis of mutations related to the tumour extracted from the patient’s circulation.

Velculescu’s 2015 study provides some insight into early detection. His research group examined the utility of circulating tumour DNA (CTDNA) in patients with pancreatic cancer. CTDNA is residual DNA that is shed from tumour cells due to their extreme activity and turnover. It contains cancer-associated mutations which can be used as a measurable indicator of the presence of a tumor. This method has the potential to be an extremely sensitive diagnostic tool, which is more rapid and less invasive than current techniques.

In another part of the study – as proof of ctdna’s potential as a reliable diagnostic tool – the research group found that almost half of the patients had detectable CTDNA. Continued detection of this CTDNA after resection (surgery) was very closely correlated to the patient’s overall outcome and chance of clinical relapse – suggesting that this type of analysis may be able to predict if the cancer will return and whether a patient will survive. Furthermore, the cancer’s return was detected six and a half months earlier using this method as opposed to standard CT imaging, which may provide clinicians with a way to detect and treat this type of cancer earlier.

In addition to the lack of available markers for pancreatic cancer, the tumours themselves are known to be very heterogeneous, meaning that different parts of a tumour can be composed of different mutations and cell types. However, CTDNA is regarded as being less widely influenced by these differences as opposed to alternative methods, such as direct biopsy – the removal of tissue for examination – and thus, it may provide a more accurate picture of what is happening to the tumour as a whole.

Hope for prevention

The conditions that increase susceptibility to pancreatic cancer remain unclear. Obesity and diabetes seem to be risk factors. In ad- dition, approximately a quarter of pancreatic cancer cases have been linked to smoking. It would thus seem clear that lots of exercise and a balanced diet is the way to go, as with any healthy lifestyle consistent with disease prevention. It is interesting to note that pancreatic cancer is more commonly seen in wealthy countries, suggesting, among other things, that our overconsumption of food combined with our concomitant lack of exercise are serious players to consider in the fight against this disease. For example, there is a positive correlation between high consumption rates of meat and dairy and the risk for pancreatic cancer.

Every day pancreatic cancer takes the lives of 12 people in Canada, and as it stands now, diagnosis might as well be a death sentence. However, new techniques for detection and treatment, such as the analysis of CTDNA, offer promise for patients. Hopefully this research can be moved into the clinic soon. This new research allows us to gain more knowledge about the signs and symptoms of pancreatic cancer. All of this may be the key to detecting this deadly disease earlier and with more accuracy.

The cancer’s return was detected six and a half months earlier using [CTDNA analysis] as opposed to standard CT imaging.