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

A method of determining the probability of a therapeutic response of a disease or disorder having an etiology associated with excessive cell proliferation in a subject having such disease or disorder, wherein the therapeutic response is to treatment of the subject with a cardiac glycoside, the method comprising:

• obtaining a sample of tissue from the subject, wherein the tissue is suspected of possessing a disease or disorder, and the tissue comprises one or more isoforms of the α subunit of Na, K-ATPase;
• 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;
• with the kit, determining the ratio of α3 isoform to α1 isoform of Na, K-ATPase 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 in vitro sample or biopsy 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 in vitro sample, and calculating the ratio thereof;
• and
• determining the probability of a therapeutic response, according to the ratio of α3 isoform to α1 isoform of Na, K-ATPase, in the subject were the subject to be treated with a therapeutically relevant dose of cardiac glycoside, wherein 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;
• and
• Probability that there will be a
• Ratio
• therapeutic response in the subject
• 0.3-0.45 +/− 0.05
• 20-<30%
• 0.5-0.95 +/− 0.05
• 30-50%
• >/=1 +/− 0.05
• >50%
• >10
• >75%
• indicating the determined probability of a therapeutic response.

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 a sample obtained from the subject, the sample comprising cellular material exhibiting a disease or disorder having an etiology associated with excessive cell proliferation;
• providing or assembling a kit suitable for determining the ratio of α3 isoform to α1 isoform of Na, K-ATPase α-subunit in the sample;
• with the kit, conducting an assay to determine the ratio of α3 isoform to α1 isoform of Na, K-ATPase α-subunit in the sample;
• 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 a
• Ratio
• therapeutic response in the subject
• 0.3-0.45 +/− 0.05
• 20-<30%
• 0.5-0.95 +/− 0.05
• 30-50%
• >/=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.