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 for treating a hematologic cancer, comprising administering a Hypoxia-Inducible Factor (HIF) inhibitor to a mammal in need thereof. 
     
     
         2 . The method of  claim 1 , wherein the HIF inhibitor is a HIF1α inhibitor. 
     
     
         3 . The method of  claim 1 , wherein the HIF inhibitor is selected from the group consisting of echinomycin, 2-methoxyestradiol, and geldanamycin. 
     
     
         4 . The method of  claim 1 , wherein the echinomycin is administered at a non-toxic dose. 
     
     
         5 . The method of  claim 4 , wherein the dose is 1-100 mcg/m 2 . 
     
     
         6 . The method of  claim 3 , 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 HIF inhibitor is coadministered with a second cancer therapy. 
     
     
         9 . The method of  claim 1 , wherein the hematological cancer is a leukemia or a lymphoma. 
     
     
         10 . The method of  claim 9 , wherein the leukemia is acute myeloid leukemia. 
     
     
         11 . The method of  claim 10 , wherein the mammal 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,s1,−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 mammal carries leukemia cells of the phenotype CD 38   − CD 34   + . 
     
     
         14 . The method of  claim 10 , wherein the mammal 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 for inducing acute myeloid leukemia remission, comprising administering echinomycin to a patient in need thereof. 
     
     
         18 . The method of  claim 17 , wherein the echinomycin is administered at a non-toxic dose. 
     
     
         19 . The method of  claim 18 , wherein the dose is 1-100 mcg/m 2 . 
     
     
         20 . (canceled) 
     
     
         21 . A method for preventing future relapse of acute myeloid leukemia, comprising administering a HIF inhibitor to a patient during remission from acute myeloid leukemia.