The Hallmarks of Pancreatic Cancer

The hallmarks of cancer and enabling characteristics are widely regarded as the key features that best define malignant disease. In a process as intricate as the development of cancer, a simple definition or stepwise series of biological events does little to encapsulate the insurmountable complexity that is this disease. Indeed, over the course of the last 25 years alone, there have been four renditions of the “ Hallmarks of Cancer ”, each attempting to encapsulate the mechanisms involved in the development of cancer by providing a list of strict criteria that must be met in order to define the disease. With each of these four sets of principles, modern research has caused the ensuing recapitulation to be revised, and without exception, to expand. In fact, what originally began as six hallmarks of cancer, has become a list of parameters that is fourteen strong, and which aim to summarize the functional capabilities that, when acquired by human cells, provides them with the ability to form a malignant, life-threatening tumour. While at present, these hallmark capabilities have largely been discussed in the context of all cancers, this review discusses each in the specific context of pancreatic cancer (PC). PC has the worst prognosis of all cancers globally, with late-stage diagnoses, aggressive tumour microenvironments, and limited treatment options contributing to the current 5-year survival rate of 13%. Here, we highlight PC-specific mechanisms underpinning each hallmark of cancer to provide a comprehensive review of the current state of knowledge around this complex disease, with the aim of aiding understanding and facilitating more meaningful research avenues. • Pancreatic cancer (PC) is the worst prognosis cancer globally • PC has an aggressive tumour microenvironment which drives these poor survival rates • The hallmarks of cancer summarise the functional characteristics which define malignancy • PC exhibits unique, specific mechanisms governing these hallmark capabilities • These mechanisms are detailed at length to facilitate more meaningful PC research