Diagnostic and prognostic assays based on circulating tyrosine kinase activity

摘要

Provided herein are methods for the diagnosis, prognosis, or management of diseases, such as cancer, by measuring the tyrosine kinase activity in acellular body fluids. Further provided are methods of predicting response to therapy in certain populations of cancer patients by contacting an acellular body fluid sample from a patient with a test agent, such as a tyrosine kinase inhibitor, and then measuring the effect of the test agent on tyrosine kinase activity in the sample.

主权项

1. A method for predicting the response of a patient with a BCR-ABL1-positive leukemia to therapy with a BCR-ABL1 kinase inhibitor, the method comprising:
(a) measuring a first level of circulating tyrosine kinase (cTK) activity in a first sample of an acellular body fluid from a patient wherein the acellular body fluid is selected from the group consisting of plasma and serum, and wherein the measuring comprises contacting the plasma or serum with one or more tyrosine kinase (TK) substrates and measuring the phosphorylation of the one or more substrates by cTKs; (b) contacting a second sample of plasma or serum from the patient with an effective amount of one or more BCR-ABL1 kinase inhibitors; (c) measuring a second level of cTK activity in the second plasma or serum sample after it has been contacted with the one or more BCR-ABL1 kinase inhibitors, wherein the measuring comprises contacting the plasma or serum with one or more tyrosine kinase (TK) substrates and measuring the phosphorylation of the one or more substrates by cTKs; and (d) comparing the first level of cTK activity to the second level of cTK activity, wherein a decrease between the first level and the second level indicates that the patient is a potential responder to therapy with the one or more BCR-ABL1 kinase inhibitors, and wherein no change between the first level and the second level indicates that the patient is potentially not a responder to therapy with the one or more BCR-ABL1 kinase inhibitors.