When asked about pancreatic cancer, physicians roll out a grim parade of statistics. Only around one in ten people survive for more than five years after diagnosis. Average survival is just four months. “It is amongst the deadliest of cancers,” says Marc Besselink, a pancreatic surgeon at the Amsterdam University Medical Center.
In the Netherlands, he says, 65% of people with pancreatic cancer do not receive treatment to target the tumour. This is not through lack of action, but because the disease is usually too advanced by the time people are diagnosed. Vague symptoms, such as back pain, unexplained weight loss and loss of appetite, mean that more than half of people will already have metastatic disease — in which the cancer has spread to other areas of the body, such as the liver and lungs — when diagnosed. Surgery is an option only if the cancer has not spread. People without metastatic disease can also receive a potent cocktail of chemotherapies. But these interventions are life-saving for only a very small minority of people.
Nature Outlook: Pancreatic cancer
Scientists are looking for better options, including cancer vaccines. Advances over the past few years have buoyed cancer biologists with enough hope that some suggest that a cure could be possible. The objective with therapeutic vaccines — which have shown promise for prostate and skin cancer — is to train a person’s immune system, after surgery and chemotherapy, to seek and destroy pancreatic cancer cells, no matter where they are. Immune memory then guards against a tumour returning.
Two strategies are at the vanguard. Both tutor the immune system to attack proteins that are more plentiful on the surface of pancreatic cancer cells than they are on other cell types. One targets changes to proteins that are specific to a person’s cancer to create a tailored vaccine, the other takes aim at subtle alterations in a protein that are hallmarks of pancreatic cancers.
People are already receiving these vaccines in early clinical trials, and companies hope to eventually roll out vaccines to hospitals. Pancreatic cancer has a reputation as a bruising opponent for new treatments, and there are many hurdles to overcome. But therapeutic vaccines would be “a game changer if they work for pancreatic cancer”, says Shivan Sivakumar, an oncologist at the University of Birmingham, UK.
A whole-body approach
The low rate of success with standard forms of treatment is only part of the reason why scientists are developing therapies. Many routine procedures have serious downsides.
Surgery, for instance, is tricky, given the pancreas’ location deep in the body and delicate nature. “You think you have this curative surgery but then one year later, half the patients are dead,” says immunologist Stephanie Dougan at Dana-Farber Cancer Institute in Boston, Massachusetts. And chemotherapy can only be used for so long — the toxicity of these drugs is not limited to cancerous cells and the resulting side effects can be difficult for people to tolerate.
The disease’s aggressive nature and tendency to spread early means that a whole-body approach that harnesses the immune system might make the most sense. Immunotherapy has already been used to successfully treat other cancers — greatly improving survival in metastatic melanoma, for example. But pancreatic cancer has proved less amenable to immune-targeted therapies. Some cancers such as melanoma have a large number of DNA mutations and therefore already attract immune cells to the tumour. Pancreatic cancers have fewer mutations and are often overlooked by patrolling immune cells. A moat of non-cancerous cells, scar tissue and blood vessels around the tumour can also impede drugs and radiotherapy.
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