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, gem citabine, resulted in a strong induction of apoptosis independent of functi onal p53, whereas the effect of either therapy atone varied between differe nt cell lines. Intratumoral injection of a helper-dependent adenovirus vect or expressing E2F1 plus drug treatment resulted in a significant reduction of tumor volume. The therapeutic effect is directly correlated with the ind uction of the p53 homologue p73, suggesting that the recently discovered E2 F1/p73 pathway plays a critical role in cancer therapy.