Pancreatic cancer is one of the most lethal human cancers with a five-year survival rate of less than 5%. Late presentation and a high level of resistance to chemotherapeutic drugs are among the major reasons for this dismal prognosis. The presence of the highest degree of desmoplasia among all solid tumours and the fact that chronic inflammatory pancreatic disease is associated with an increased risk for pancreatic cancer indicate that the tumour microenvironment is of particular importance for carcinogenesis in the pancreas.
Incidence & treatment
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most difficult cancers to treat. It is the commonest cancer affecting the exocrine pancreas.
- In 2000, there were 217,000 new cases of pancreatic cancer and 213,000 deaths world wide and 60 139 new patients (10.4% of all digestive tract cancers) and 64 801 deaths in Europe
- These figures indicate that, due to the fact that most patients will die within one year of diagnosis, incidence equals mortality.
- Without active treatment, metastatic pancreatic cancer has a median survival of 3–5 months and 6–10 months for locally advanced disease, which increases to around 11–15 months with resectional surgery
- The late presentation and aggressive tumour biology of this disease determine that only a minority (10–15%) of patients can undergo potentially curative resection.
- Major advances in the past decade are based on a decrease in surgical mortality and morbidity through the development of specialist regional centres and a modest increase in survival due to the use of systemic chemotherapy
- Currently, the therapeutic armamentarium for pancreatic cancer consists of conventional chemotherapeutic agents such as gemcitabine and 5-fluorouracil, which have been shown to offer a marginal survival benefit for patients with advanced disease
- In the adjuvant setting, survival can be extended to a median of 20-22 months
- Moreover, unlike other cancer entities such as colon cancer, molecular targeted therapies have so far largely failed to positively impact patient survival in pancreatic cancer
Failure of therapeutic approaches
- A plenitude of chemotherapeutic agents and novel molecular targeted therapies addressing epithelial tumour cells, all showing antitumour activity in cell culture and mouse experiments, have failed to show significant effects in clinical pancreatic cancer trials.
- Thus, it appears that therapeutic approaches targeting pancreatic tumour cells alone are unlikely to improve the prognosis of pancreatic cancer.
Importance of the tumour microenvironment
- Evidence accumulated during recent years for multiple tumours has clearly demonstrated that the tumour microenvironment comprising stroma, blood vessels, infiltrating inflammatory cells and a variety of associated tissue cells are of paramount importance in regulating proliferating tumour cells including a subpopulation of cancer stem cells and thus determine tumour aggression and chemoresistance.
- The presence of the highest degree of desmoplasia among all solid tumours and the fact that chronic inflammatory pancreatic disease is associated with an increased risk for pancreatic cancer in both human and mouse models indicate that the tumour microenvironment seems to be of particular importance for carcinogenesis in the pancreas.