Compositions and methods for drug-sensitization or inhibition of a cancer cell

Abstract

The disclosure provides rifamycin and rifamycin derivative compositions, including rifabutin and rifabutin derivative compositions able to cause drug-sensitization in a cancer cell or inhibition of a cancer cell. The disclosure also provides methods of administering such compositions to cancer cells to sensitize them to drugs, such as chemotherapeutics, or directly inhibit them. The disclosure also provides methods of administering such compositions to increase reactive oxygen species (ROS), particularly superoxides, in cancer cells. The disclosure further provides methods of determining whether a cancer will respond to chemotherapeutics and whether to administer rifamycin or a rifamycin derivative based on ROS levels in cancer cells of a patient.

1 .- 38 . (canceled) 
     
     
         39 . A method of determining whether to administer rifamycin or rifamycin derivative to a patient with cancer comprising:
 obtaining a cancer cell sample from the patient;   measuring the reactive oxygen species (ROS) amount in the sample; and   determining if the ROS amount is abnormally low for the cancer cell type,   wherein an abnormally low ROS level indicates administration of rifamycin or rifamycin derivative to the patient.   
     
     
         40 . The method of  claim 39 , wherein the ROS comprises a superoxide. 
     
     
         41 . The method of  claim 39 , further comprising additionally determining whether to administer a drug to the patient in addition to rifamycin or a rifamycin derivative. 
     
     
         42 . The method of  claim 41 , wherein the drug comprises a chemotherapeutic. 
     
     
         43 . The method of  claim 42 , wherein the cancer cell comprises a cancer cell resistant to the drug. 
     
     
         44 . The method of  claim 42 , wherein the chemotherapeutic drug comprises an alkylating agent, an antimetabolite, an anti-tumor antibiotic, a hormonal agent, a targeted therapy, or a differentiating agent. 
     
     
         45 . The method of  claim 39 , wherein rifamycin or a rifamycin derivative has been previously administered to the patient, and determining comprises determining whether to administer rifamycin or a rifamycin derivative to the patient a second or greater time. 
     
     
         46 . The method of  claim 39 , wherein the cancer cell is a carcinoma, a sarcoma, a leukemia, a lymphoma, or a glioma. 
     
     
         47 . The method of  claim 39 , wherein the cancer cell is a metastatic cancer cell. 
     
     
         48 . The method of  claim 39 , wherein the ROS comprises a superoxide. 
     
     
         49 . The method of  claim 39 , wherein the rifamycin derivative comprises a rifabutin derivative. 
     
     
         50 . The method of  claim 49 , wherein the rifabutin derivative has the following formula: 
       
         
           
           
               
               
           
         
         wherein R is an alkyl, aryl, or hetero-aryl group. 
       
     
     
         51 . The method of  claim 49 , wherein the rifabutin derivative has the following formula: 
       
         
           
           
               
               
           
         
         wherein R is an alkyl, aryl, or hetero-aryl group. 
       
     
     
         52 . The method of  claim 51 , wherein R comprises one of the following structures: 
       
         
           
           
               
               
           
         
       
     
     
         53 . The method of  claim 52 , wherein R comprises one of the following structures: 
       
         
           
           
               
               
           
         
       
     
     
         54 . The method of  claim 49 , wherein the rifabutin derivative has the following formula: 
       
         
           
           
               
               
           
         
         wherein X is a C, O, or N and R is an alkyl, aryl, or hetero-aryl group. 
       
     
     
         55 . The composition of  claim 54 , wherein R comprises one of the following structures: 
       
         
           
           
               
               
           
         
       
     
     
         56 . The method of  claim 49 , wherein the rifabutin derivative has the following formula: 
       
         
           
           
               
               
           
         
         wherein X is a C, O, or N and R is an alkyl, aryl, or hetero-aryl group. 
       
     
     
         57 . The method of  claim 56 , wherein R comprises one of the following structures: 
       
         
           
           
               
               
           
         
       
     
     
         58 . The method of  claim 49 , wherein the rifabutin derivative has the following formula: 
       
         
           
           
               
               
           
         
         wherein R comprises one of the following structures: 
       
       
         
           
           
               
               
           
         
       
     
     
         59 . The method of  claim 49 , wherein the rifabutin derivative has the following formula: 
       
         
           
           
               
               
           
         
         wherein R comprises 
       
       
         
           
           
               
               
           
         
       
     
     
         60 . The method of  claim 49 , wherein the rifabutin derivative has the following formula: 
       
         
           
           
               
               
           
         
         wherein X is a C, O, or N and R is an alkyl, aryl, or hetero-aryl group. 
       
     
     
         61 . The method of  claim 60 , wherein R comprises one of the following structures: 
       
         
           
           
               
               
           
         
       
     
     
         62 . The method of  claim 49 , wherein the rifamycin or rifamycin derivative further comprises a pharmaceutically acceptable carrier, a salt, a buffer, a preservative, or a solubility enhancer.