Uses of hypoxia-inducible factor inhibitors

Abstract

The present invention relates to treating a hematologic cancer using a Hypoxia-Inducible Factor (HIF inhibitor). The invention also relates to inducing acute myeloid leukemia remission using the HIF inhibitor. The invention further relates to inhibiting a maintenance or survival function of a cancer stem cell (CSC) using the HIF inhibitor.

1 . A method of treating a leukemia or lymphoma in a human subject in need thereof, comprising administering echinomycin to the subject. 
     
     
         2 .- 3 . (canceled) 
     
     
         4 . The method of  claim 1 , wherein the echinomycin is administered at a dose and interval to maintain a serum concentration of echinomycin of less than or equal to 5 nM. 
     
     
         5 . (canceled) 
     
     
         6 . The method of  claim 1 , wherein the echinomycin is coadministered with a Hedgehog pathway inhibitor. 
     
     
         7 . The method of  claim 6 , wherein the Hedgehog pathway inhibitor is cyclopamine. 
     
     
         8 . The method of  claim 1 , wherein the echinomycin is coadministered with a second cancer therapy. 
     
     
         9 . (canceled) 
     
     
         10 . The method of  claim 1 , wherein the treatment is for the leukemia, and wherein the leukemia is acute myeloid leukemia. 
     
     
         11 . The method of  claim 10 , wherein the subject carries a cytogenetic alteration. 
     
     
         12 . The method of  claim 11 , wherein the cytogenetic alteration is selected from the group consisting of:
 47,XY, +21; 46,XY;   45,XX, −7;   46,XY,t(8; 21)(q22; q22);   49,XX, +8, +8,inv(16)(p13.1q22), +21;   46,XX,inv(16)(p13q22)/46,XX;   46,XY,inv(16)(p13q22);   46,XX,t(2; 13)(p23; q12)/46,XX;   45,XY,inv(3)(q21q26.2), −7/46,XY;   47,XY, +4,inv(5)(p15q13)/47,sl, −4, +22;   46,XX,t(11; 19)(q23; p13.1);   46,XX,t(6; 11)(q27; q23)/46,XX; and   46,XX,t(1; 17)(p13; q25),t(9; 11)(p22; q23).   
     
     
         13 . The method of  claim 9 , wherein the subject carries leukemia cells of the phenotype CD38−CD34+. 
     
     
         14 . The method of  claim 10 , wherein the subject carries cancer stem cells. 
     
     
         15 . The method of  claim 14 , wherein the cancer stem cells are multiple drug resistant. 
     
     
         16 . The method of  claim 14 , wherein the cancer stem cells are chemoresistant or radioresistant. 
     
     
         17 . A method of inducing acute myeloid leukemia remission in a human patient in need thereof, comprising administering echinomycin to the patient. 
     
     
         18 . The method of  claim 17 , wherein the echinomycin is administered at a dose and interval to maintain a serum concentration of echinomycin of less than or equal to 5 nM. 
     
     
         19 .- 20 . (canceled) 
     
     
         21 . A method of preventing future relapse of acute myeloid leukemia in a human patient in need thereof, comprising administering echinomycin to the patient during remission from acute myeloid leukemia. 
     
     
         22 . The method of  claim 21 , wherein the echinomycin is administered at a dose and interval to maintain a serum concentration of echinomycin of less than or equal to 5 nM. 
     
     
         23 . The method of  claim 4 , wherein the maintained serum concentration is 0.01 to 5 nM. 
     
     
         24 . The method of  claim 18 , wherein the maintained serum concentration is 0.01 to 5 nM. 
     
     
         25 . The method of  claim 22 , wherein the maintained serum concentration is 0.01 to 5 nM.