Pancreatic ductal adenocarcinoma (PDA) is among the most deadly cancers with less than 5% of the patients living beyond 5 years post-diagnosis. Lack of early diagnostic biomarkers and resistance to current therapies help explain these disappointing numbers. Thus, more effective and better-targeted therapies are needed quickly. Monoclonal antibodies offer an attractive alternative targeted therapy option for PDA because they are highly specific and potent. However, currently available monoclonal antibody therapies for PDA are still in their infancy with a low success rate and low likelihood of being approved. The challenges faced by these therapies include the following: lack of predictive and response biomarkers, unfavorable safety profiles, expression of targets not restricted to the cancer cells, flawed preclinical model systems, drug resistance, and PDA's complex nature. Additionally, discovery of novel PDA-specific antigen targets, present on the cell surface or in the extracellular matrix, is needed. Predictive and response markers also need to be determined for PDA patient subgroups so that the most appropriate effective therapy can be delivered. Serologic approaches, recombinant antibody-producing technologies, and advances in antibody engineering techniques will help to identify these predictive biomarkers and aid in the development of new therapeutic antibodies. A combinatorial approach simultaneously targeting antigens on the PDA cell, stroma, and immunosuppressive cells should be employed.
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