Early diagnosis of disease allows for more effective therapy and better clinical outcomes. In cancer, extensive effort has gone toward development of screening and diagnostic techniques for early detection of disease. Despite this effort, the probability of single-analyte assays providing the """"""""silver bullet"""""""" to address these problems for any specific tumor is vanishingly small. A more comprehensive approach that is more likely to succeed is the development of an integrated molecular diagnostic system using multiplexed assays of cancer-related biomarkers coupled with data analysis using bioinformatics-based algorithms. The development of multiplexed assays to improve quality of patient life is a major goal of SomaLogic. SomaLogic's proprietary nucleic-acid based capture agents, photoaptamers, yield quantitative analysis of proteins found in complex biological samples. Using data generated with this assay platform, we expect to develop predictive biomedical algorithms for the diagnosis and management of a variety of diseases, including cancer. The specific objective of this Phase I proposal is to develop an initial set of photoaptamers targeted to proteins and/or protein complexes that have been associated with a wide variety of solid tumors, i.e., proteinases, proteinase inhibitors, and proteinase-inhibitor complexes, which can then be used to screen clinical samples from patients with a variety of solid tumor types and stages of disease.
The specific aims of the proposed research are to: 1) develop a set of well-defined photoaptamers specific for 20 proteinases, antiproteinases and proteinase-antiproteinase complexes that are believed to be associated with invasion and metastasis of solid tumors; 2) develop a photoaptamer microarray assay (""""""""proteomics chip"""""""") for the measurement of at least 20 cognate proteins or protein complexes in serum or plasma; and 3) evaluate the ranges for these proteins or protein complexes in serum and plasma obtained from normal subjects. The overall objective of our research efforts in cancer is to develop CLIA-compatible assays and algorithm-based analysis systems for the monitoring of patients at risk for or diagnosed with various malignancies using aptamers directed against proteins that are either generally associated (proteinases, antiproteinases, adhesion molecules chemokines and/or chemokine receptors) or specifically associated (known cell markers, tissue specific proteins, transcriptional regulators, etc.) with solid tumors.
