Pancreatic cancer: translating lessons from mouse models

Pancreatic cancer is the 10th most common cancer and 4th cause of cancer related deaths. Progress in diagnosis and treatment has been slow and disappointing but improvement in understanding of pathogenesis and of molecular changes may offer some ground for rational and etiological approach. During the last ten years the first evidence about the benefit of targeting dysregulated pathways was provided by the study that tried the addition of the EGFR inhibitor erlotinib to the standard cytotoxic gemcitabine. Since then, despite other numerous negative studies, various agents have been investigated in the preclinical and clinical setting and are currently through drug development pipeline. In this year's Gastrointestinal Symposium of the American Society of Clinical Oncology (GI ASCO, San Francisco, 15-17 January 2009), translational and clinical researchers presented evidence of specific genetic variations predicting toxicity (Abstract #115) or efficacy (Abstract #118) of gemcitabine-based treatment and of clinical biomarkers which may serve as predictors of therapy (Abstract #117) or mortality (Abstract #202). We were also informed about the presence of a new surface antigen (CD133) in pancreatic cancer stem cells (Abstract #150) and the development of a recombinant viral vector carrying the G antigen 1 (GAGE1) gene able for B-cells transduction (Abstract #178), which may lead potentially to the development of new immunotherapies and targeted agents. Study and efficacy of novel targeted molecules in preclinical models in vitro and in vivo was also presented (Abstracts #144, 145, 158, 163). In contrast to other malignancies, no mutations of the EGFR/PI3K pathway were found in pancreatic cancer cells not allowing thus a patients' selection approach for EGFR antibodies (Abstract #173).