Compositions and methods for inhibiting cancer stem cells

Abstract

The disclosure generally provides compositions and methods that are useful in the treatment of cancer. More specifically, the methods and compositions may be used to detect, quantify, inhibit, kill, differentiate, or eliminate cancer stem cells (CSCs) and may be used in the treatment of cancers associated with CSCs, and particularly cancers and CSCs that express LOX1.

We claim: 
     
         1 . A method for inhibiting proliferation of a cancer stem cell (CSC) comprising contacting the CSC with an inhibitor of Lectin-like oxidized LDL receptor 1 (LOX1) in an amount effective to inhibit proliferation of the CSC. 
     
     
         2 . The method of  claim 1  wherein the CSC expresses LOX1. 
     
     
         3 . The method of  claim 1  wherein the CSC is a sphere-forming CSC. 
     
     
         4 . The method of  claim 1  wherein the CSC is from a cancer selected from the group consisting of colorectal cancer, pancreatic cancer, lung cancer, head and neck cancer, gastric cancer, hepatocellular carcinoma, and breast cancer. 
     
     
         5 . The method of  claim 1  wherein the inhibitor is selected from the group consisting of an antibody that binds LOX1, a small molecule inhibitor of LOX1, and a siRNA that hybridizes to a nucleic acid encoding LOX1. 
     
     
         6 . A method for treating a therapeutically-resistant cancer in a subject who has previously received a therapy and who is in need of treatment, comprising administering to the subject an inhibitor of LOX1 in an amount effective to inhibit or kill cancer stem cells (CSCs) present in the therapeutically-resistant cancer. The method of  claim 6  wherein the CSCs express LOX1. 
     
     
         8 . The method of  claim 6  wherein the CSCs comprise sphere-forming CSCs. 
     
     
         9 . The method of  claim 6  wherein the CSCs are from a cancer selected from the group consisting of colorectal cancer, pancreatic cancer, lung cancer, head and neck cancer, gastric cancer, hepatocellular carcinoma, and breast cancer. 
     
     
         10 . The method of  claim 6  wherein the inhibitor is selected from the group consisting of an antibody that binds LOX1, a small molecule inhibitor of LOX1, and a siRNA that hybridizes to a nucleic acid encoding LOX1. 
     
     
         11 . A method for treating cancer in a subject who has recurring or relapsed cancer comprising administering to a subject an inhibitor of LOX1 in an amount effective to inhibit or kill CSCs in the cancer. 
     
     
         12 . The method of  claim 11  wherein the CSCs express LOX1. 
     
     
         13 . The method of  claim 11  wherein the CSCs comprise sphere-forming CSCs. 
     
     
         14 . The method of  claim 11  wherein the CSCs are from a cancer selected from the group consisting of colorectal cancer, pancreatic cancer, lung cancer, head and neck cancer, gastric cancer, hepatocellular carcinoma, and breast cancer. 
     
     
         15 . The method of  claim 11  wherein the inhibitor is selected from the group consisting of an antibody that binds LOX1, a small molecule inhibitor of LOX1, and a siRNA that hybridizes to a nucleic acid encoding LOX1. 
     
     
         16 . The method of  claim 15  wherein the inhibitor is an antibody that binds LOX1. 
     
     
         17 . A method for inhibiting, reducing, or preventing chemotherapy-associated cardiotoxicity in a patient in need of chemotherapy comprising administering to the patient an inhibitor of LOX1 in an amount effective to inhibit, reduce, or prevent chemotherapy-associated cardiotoxicity. 
     
     
         18 . The method of  claim 17  wherein the chemotherapy is an anthracycline. 
     
     
         19 . The method of  claim 17  wherein the inhibitor is selected from the group consisting of an antibody that binds LOX1, a small molecule inhibitor of LOX1, and a siRNA that hybridizes to a nucleic acid encoding LOX1. 
     
     
         20 . The method of  claim 19  wherein the inhibitor is an antibody that binds LOX1.