Method of determining the probability of a therapeutic response in cancer chemotherapy with cardiac glycoside

摘要

A prognostic assay and kit and method of use thereof are provided. The kit and assay are used to determine the likelihood of a diseased cell or tissue having a therapeutic response to treatment with a cardiac glycoside in a disease having an etiology associated with excessive cell proliferation. The kit and assay are used to determine the ratio of isoforms of the α subunit of Na, K-ATPase obtained from the diseased cell or tissue. The kit can be used to predict the therapeutic responsiveness of cancer or tumor in a subject to treatment with a cardiac glycoside. The kit and assay can be incorporated in a method of treating a disease or disorder having an etiology associated with excessive cell proliferation with a composition comprising a cardiac glycoside.

主权项

1. A method of determining whether a subject having a disease or disorder having an etiology associated with excessive cell proliferation should be treated with a cardiac glycoside, the method comprising:
providing or assembling a kit comprising at least the following components: a) a first primary antibody having a binding affinity for the α3 subunit isoform of Na, K-ATPase; and b) a second primary antibody having a binding affinity for the α-1 subunit isoform of Na, K-ATPase; obtaining a sample of tissue from the subject, the tissue exhibiting a disease or disorder having an etiology associated with excessive cell proliferation, the sample comprising one or more isoforms of the αsubunit of Na, K-ATPase; with the kit, determining the ratio of α3 isoform to α1 isoform of Na, K-ATPase α-subunit in the sample, wherein the step of determining the ratio comprises: a) quantifying the level of expression of each the α3 subunit isoform of Na, K-ATPase and the α1 subunit isoform of Na, K-ATPase in the sample, and calculating the ratio thereof; or b) determining the amount of the α3 subunit isoform of Na, K-ATPase relative to amount of the α1 subunit isoform of Na, K-ATPase in the sample, and calculating the ratio thereof;
wherein according to the ratio of α3 isoform to α1 isoform of Na, K-ATPase, were the subject to be treated with a therapeutically relevant dose of cardiac glycoside, the probability that there will be at least a partial therapeutic response is related to the ratio of α3 isoform to α1 isoform of Na, K-ATPase according to the following table;Probability that there will be aRatiotherapeutic response in the subject0.3-0.45 +/− 0.0520-<30%0.5-0.95 +/− 0.0530-50%  >/=1 +/− 0.05>50%>10>75%and
if the ratio is ≧0.3, indicating the subject should be treated with cardiac glycoside by administration of a composition comprising cardiac glycoside to the subject, or if the ratio is <0.3, indicating the subject should not be treated with cardiac glycoside for treatment of the disease or disorder having an etiology associated with excessive cell proliferation.