title: Monoclonal antibody therapies targeting pancreatic ductal adenocarcinoma.
abstract: Pancreatic ductal adenocarcinoma (PDA) is a lethal disease with a poor prognosis where incidence mirrors mortality. Gemcitabine and gemcitabine plus erlotinib (epidermal growth factor receptor tyrosine kinase inhibitor) are the only FDA approved therapies for unresectable or metastatic PDA and are at best palliative. Hence, considerable efforts have been initiated to identify novel targets for monoclonal antibody (Mab) therapies that may safely and effectively be combined with gemcitabine. Mabs to cell surface receptors and/or their ligands have shown efficacy in pre-clinical and clinical studies in both solid and hematological malignancies and can safely be given with chemotherapy. A number of clinical trials have evaluated the safety and efficacy of Mabs targeting the tumor and/or tumor micro-environment and in combination with chemotherapy for PDA with very little success. Here we review the rationale for Mab therapies, targeted clinical trials, rational basis for target selection, pre-clinical models and promising novel cell surface targets and/or growth factor ligands that are amenable to ongoing and future Mab therapies that hold promise and hope for patients and their families with this devastating disease.
authors: Arizona Cancer Center, Tucson, AZ 85724, USA.
authors: Kevin
authors: K
authors: Engelhardt
authors: Christopher
authors: C
authors: Riley
authors: Laurence
authors: L
authors: Cooke
authors: Daruka
authors: D
authors: Mahadevan
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy* / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D009363:Neoplasm Proteins / Q000276:immunology / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D036341:Intercellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D011956:Receptors, Cell Surface