Surface receptor complexes as biomarkers

Abstract

The present invention relates to a new class of biomarkers in patient samples comprising dimers of cell surface membrane receptors. In one aspect, the invention includes a method of assaying a disease state or health condition wherein such condition is dimerized with one or more cell surface membrane receptors measured directly in a patient sample, particularly a fixed tissue sample related to the volume of the body. In another aspect, the invention includes a method of determining the status of cancer in a sample from an individual, wherein a measurement of the amount of one or more cell surface receptor dimers in cells of the sample is correlated with the status, including cancer Presence or absence of a pre-cancerous state, presence or absence of a cancerous state, cancer prognosis, or responsiveness to treatment. Preferably, the methods of the invention are carried out by employing panels of binding compounds with releasable molecular tags specific for various components of one or more types of receptor dimers.

Description

field of invention [0001] The present invention relates generally to biomarkers and, in particular, to the use of cell surface receptor complexes, such as dimers or oligomers, as biomarkers Background of the invention [0002] A biomarker is a characteristic that can be objectively measured and calculated as an indicator of a normal biological process, a pathogenic process, or a pharmacological response to a therapeutic intervention, Atkinson et al., Clin.Pharmacol.Ther., 69 : 89-95 (2001). Biomarkers vary widely in nature, ease of measurement, and relationship to the physiological state of the target, eg Frank et al., Nature Reviews Drug Discovery, 2: 566-580 (2003). It is widely believed that the development of novel and effective biomarkers can both significantly reduce the cost of healthcare and drug development and greatly improve the treatment of a wide variety of diseases and conditions. To this end, people have made a lot of efforts to use...

AI Technical Summary

Problems solved by technology

Although receptor dimerization plays an important role in cellular and disease processes, expression of receptor dimers has not been adopted as a biomarker, in part due to the inconvenience and lack of sensitivity of current measurement techniques, and the inability to or cannot practically use this technique to measure formalin-fixed and / or patient samples that are too small for analysis, e.g. Price et al., Methods in Molecular Biology, 218:255-267 (2003); Stagljar , Science STKE 2003, pe56 (2003); Koll et al., International Patent Publication WO 2004 / 008099; Golemis, editor, Protein-Protein Interactions (Cold Spring Harbor Laboratory Press, New York, 2002); Sorkin et al., Curr.Biol., 10 : 1395-1398 (2000); McVey et al., J.Biol.Chem., 17: 14092-14099 (2001); Salim et al., J.Biol.Chem., 277: 15482-15485 (2002); Angers et al., Annu .Rev.Pharmacol.Toxicol., 42:409-435 (2002); Szollosi et al., Reviews in Molecular Biotechnology, 82:251-266 (2002); Matko et al., Meth.in Enzymol., 278:444-462 (1997) ; U.S. Patent 5,192,660 to Reed-Gitomer

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