Pancreatic ductal adenocarcinoma (PDAC) remains a major unsolved health problem. 
As conventional treatments have shown only a modest impact on disease course, 
development of new therapeutic strategies based on the molecular biology of PDAC 
must be a high priority. The identification of relevant predictive and 
prognostic biomarkers which can be used to select patient subgroups that may 
benefit from conventional treatments and new targeted agents will be of 
considerable interest. We have demonstrated the ability of the metabolizing 
gemcitabine protein (the human Equilibrative nucleoside transporter 1 and the 
deoxycytidine kinase) in predicting the benefit of adjuvant gemcitabine-based 
therapy in resected PDAC patients. Beside these predictive biomarkers, we have 
evaluated different molecular factors that may impact on the likely course of 
this cancer. The chemokine receptor CXCR4 that has been shown to be implicated 
in PDAC tumorigenicity and aggressiveness could serve as a prognostic marker for 
survival after a curative-intent surgery and was associated with the pattern of 
tumour recurrence (distant versus local relapse). Our findings were validated in 
an independent cohort of patients. Overall our results suggested that (i) the 
benefit of an adjuvant gemcitabine-based therapy can be predicted based on the 
tumour expression of hENT1 and dCK, (ii) CXCR4 is an independent negative 
prognostic factor and an independent predictor of distant relapse suggesting 
that anti-CXCR4 targeting therapies can be a promising treatment in combination 
with cytotoxic chemotherapy in the adjuvant setting. These data open new 
perspectives for designing trials based on a molecular driven strategy.