Biliopancreatic malignancy: future prospects for progress.

Several key areas are targeted by novel therapies. Growth factors and their receptors are overexpressed in a high percentage of pancreatic tumors. These factors are critical to tumor cell growth and development. They also promote tumor growth by stimulating angiogenesis. Mutations in other molecules that regulate cell growth, such as the ras protein and the tumor suppressor p53, contribute to a state of continuously stimulated cell proliferation. Other types of molecules such as mucins are also altered or overexpressed in tumors. Mucins are immunosuppressive and are important in tumor cell metastasis. A number of promising new therapeutic strategies are now being tested. Ribozymes or antisense nucleic acids can prevent synthesis of growth factor receptors or ras protein. Monoclonal antibodies block interaction between receptor and its ligand. Newly developed drugs prevent tyrosine phosphorylation of growth factor receptors or farnesylation of ras protein. Gene therapy is another approach that is under investigation. Transduction or transfection of genes for wild-type tumor suppressors could correct defects in growth regulation. Vaccines developed against tumor antigens provide hope for the control of not only the primary tumor, but also of the metastatic lesions as well.