Pancreatic cancer: Prevention, detection and treatment

An incidence rate nearly equal to its mortality rate demonstrates the aggressiveness and lethal nature of pancreatic ductal adenocarcinoma (PDAC). Most patients present with advanced disease (i.e., locally-advanced or metastatic) at diagnosis, and survival rate has not improved in the last decade, with less than 7% of patients alive five years after diagnosis. Such dismal outcome can be explained by the lack of biomarkers for early screening/diagnosis, together with the aggressive biological behavior, characterized by early metastatic spread and resistance to currently available chemotherapy regimens. The therapeutic failure can also be attributed to the inter-/intra- tumor genetic heterogeneity and tumor stroma that occupies the majority of the tumor mass. Gemcitabine is being used in the treatment of PDAC, however, the response rate is less than 12%. A recent phase III trial showed that the combination of oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) is an option for the treatment of metastatic PDAC patients with good performance status, while another phase III trial showed that Abraxane plus gemcitabine had better antitumor activity with respect to gemcitabine alone. Although these therapeutic strategies are associated with increased toxicity. Further studies are warranted to develop innovative anticancer drugs that either improve gemcitabine activity, within novel combinatorial regimens, or with a better efficacy than gemcitabine. The aim of current chapter is to give an introductory overview of this dismal disease. This introduction will first elucidate the clinical presentation and management of PDAC, with a brief description of the anatomy of pancreas, as well as of epidemiology and risk factors. We will then provide a brief summary on PDAC treatment and genetic alterations found in PDAC.