Her signaling in pancreatic cancer

Pancreatic cancer remains a treatment-refractory cancer. Standard therapy for metastatic cancer is gemcitabine chemotherapy, with a median survival of5 – 6 months. The epidermal growth factor receptor (EGFR) is commonly expressed in pancreatic cancer and has been evaluated as a therapeutic target. A Phase III trial of gemcitabine with or without the EGFR inhibitor, erlotinib, demonstrated a modest but significant prolongation of survival with the addition of erlotinib. A Phase II trial of gemcitabine with the anti-EGFR antibody cetuximab resulted in a 1-year survival of 32%. A Phase III trial of gemcitabine with or without cetuximab and a randomized Phase II trial of the Murren regimen with or without cetuximab are completed; results for both are anticipated in 2007. A Phase I trial of gemcitabine with the EGFR/Her-2 inhibitor, lapatinib, is completed. Improved patient selection and rational combination of targeted therapies will be necessary to optimize the management of patients with this tragic disease.