Due to the exceptional biological complexity, heterogeneity and adaptability of human tumors, many investivational drugs in oncology has low response rates in cancer patients. These present a significant hurdle in drug development. One approach of overcoming this problem is to select a subset of patients who are likely to benefit from the therapy. In this study, from an exploratory oncology trial we identified a set of plasma protein makers by label-free protein profiling that differentiated responders from non-responders.

Plasma samples were collected from patients treated with an investigational drug. Following removal of the top 12 abundant proteins in plasma by affinity depletion, the samples were digested by trypsin. The resulting peptides were analyzed by high resolution LC-MS. Peptides with abundance significantly different between the responder and non-responder groups were sequenced by LC-MS/MS and their corresponding proteins were identified by data base searching

A set of plasma proteins had expression levels significantly different between the responders and non-responders (p < 0.0001). These markers were in a signaling pathway closely related to the drug target. These results suggested that tumor cells might be unresponsive to the inhibition of the drug target due to the presence of parallel signaling pathways

This work demonstrated the feasibility of using plasma proteins as biomarkers to select for cancer patients who would likely respond to the investigational drug