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

A method of determining the probability that a disease or disorder having an etiology associated with excessive cell proliferation, in a subject having such disease or disorder, will be at least partially therapeutically responsive to treatment with a cardiac glycoside, the method comprising:

• a) determining the ratio of α3 isoform to α1 isoform of Na, K-ATPase in a sample obtained from diseased cellular tissue of the subject, the sample comprising one or more isoforms of the α-subunit of Na, K-ATPase, wherein the step of determining said ratio comprises quantifying the level of expression of each of 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 the step of determining the ratio comprises determining the amount of each 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
• b) determining the probability of a therapeutic response according to said 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 said 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:
• Probability that there will be at least a
• Ratio
• partial 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%.

A method of determining whether or not 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:

• obtaining a sample of diseased tissue from the subject, the disease having an etiology associated with excessive cell proliferation, and the sample comprising one or more isoforms of the α-subunit of Na, K-ATPase;
• determining the ratio of α3 isoform to α1 isoform of the α-subunit of Na, K-ATPase in the sample, wherein the step of determining said ratio comprises quantifying the level of expression of each of 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 the step of determining the ratio comprises determining the amount of each 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
• if said ratio is ≧0.3, the subject should be treated with said cardiac glycoside by administration of a composition comprising said cardiac glycoside to the subject according to a prescribed dosing regimen, or
• if said ratio is <0.3, the subject should not be treated with said cardiac glycoside for treatment of said disease or disorder having an etiology associated with excessive cell proliferation.