Therapeutic efficacy of E2F1 in pancreatic cancer correlates with TP73 induction.

Pancreatic cancer is particularly resistant to apoptosis by antineoplastic agents, which is partly attributable to the lack of functional p53. Here we show that E2F1 in combination with the most clinically efficient drug, gemcitabine, resulted in a strong induction of apoptosis independent of functional p53, whereas the effect of either therapy alone varied between different cell lines. Intratumoral injection of a helper-dependent adenovirus vector expressing E2F1 plus drug treatment resulted in a significant reduction of tumor volume. The therapeutic effect is directly correlated with the induction of the p53 homologue p73, suggesting that the recently discovered E2F1/p73 pathway plays a critical role in cancer therapy.