Introduction: Previous attempts to use individual aptamers as diagnostic reagents have failed to consistently achieve
performance comparable to antibodies. Here we report a novel systems biology approach, called Adaptive Dynamic Artificial Poly-ligand Targeting (ADAPT) using poly-ligand aptamer libraries to identify responders and non-responders to trastuzumab based regimens in metastatic breast cancer. To overcome the fundamental limitation of individual aptamer binding affinities, large libraries (106 species) were created so that potentially thousands of aptamers could bind to each of a multitude of targets related to trastuzumab response or non-response.