Cancer treatment and diagnosis

Abstract

The present disclosure provides, in general, a method for selecting a therapy for treating cancer in a human subject and subsequently treating cancer in a subject, which includes isolating a cancer cell from a human subject having cancer, determining the functional activity of STING or cGAS in the cell; and selecting a therapy for the cancer based on the functional activity of the STING or cGAS in the cell. Also provided, if the functional activity of STING and/or cGAS is determined to be defective in the cell, the therapy selected is one that is effective at killing STING-deficient and/or cGAS-deficient cancer cells, e.g., therapy including administering to the subject an oncolytic virus.

What is claimed is: 
     
         1 . A method for treating cancer in a human subject, the method comprising the steps of:
 isolating a sample from a human subject having cancer;   determining the functional activity of STING in the sample;   selecting a therapy for the cancer based on the functional activity of the STING in the sample; and   treating the subject with the selected therapy.   
     
     
         2 . The method of  claim 1 , wherein the functional activity of STING is determined to be defective in the cell, and the therapy selected is one that is effective at killing STING-deficient cancer cells. 
     
     
         3 . The method of  claim 1 , wherein the subject has failed at least one chemotherapy regimen. 
     
     
         4 . The method of  claim 3 , wherein the chemotherapy regimen comprises administering to the subject an agent which causes DNA mutations. 
     
     
         5 . The method of  claim 2 , wherein the selected therapy comprises administering to the subject an oncolytic virus. 
     
     
         6 . The method of  claim 5 , wherein the oncolytic virus is derived from herpes simplex virus, vaccinia virus or Varicella Zoster virus. 
     
     
         7 . The method of  claim 1 , wherein the step of determining the functional activity of STING in the sample comprises analyzing the amount of cGAS in the cell. 
     
     
         8 . A method for treating a cancer in a human subject, the method comprising the steps of:
 determining the functional activity of STING in a sample; and   if the sample has defective STING activity, administering an oncolytic virus to the subject.   
     
     
         9 . The method of  claim 8 , wherein the step of determining the functional activity of STING in the sample comprises analyzing the amount of cGAS in the cell. 
     
     
         10 . A method for treating a cancer in a human subject, the method comprising the steps of:
 determining the functional activity of STING in a sample from the subject having the cancer; and   if the sample does not have defective STING activity, administering a cancer treatment to the subject that does not cause DNA mutation.   
     
     
         11 . A method for treating cancer in a human subject, the method comprising the steps of:
 isolating a sample from a human subject having cancer;   determining the functional activity of cGAS in the sample;   selecting a therapy for the cancer based on the functional activity of the cGAS in the sample, and   administering the selected therapy to the subject.   
     
     
         12 . A method for treating cancer comprising
 a) administering a viral oncolytic therapy to a subject,   b) determining the level of STING or cGAS in a sample from the subject, wherein a decrease in STING or cGAS activity is predictive of a positive outcome of oncolytic therapy, and   c) i) if levels of STING in the subject are low, continuing oncolytic therapy; or ii) if STING or cGAS levels are normal or partially active, discontinuing viral oncolytic therapy and/or administering a second agent that can increase STING levels in the subject in order to improve the outcome of the viral oncolytic therapy.   
     
     
         13 . The method of  claim 12 , wherein the viral oncolytic therapy comprises herpesvirus, Varicella Zoster virus or vaccinia virus. 
     
     
         14 . The method of any one of the preceding claims, wherein the cancer is selected from the group consisting of colorectal cancer, colitis-associated cancer and melanoma. 
     
     
         15 . The method of any one of the preceding claims, wherein the sample is a body fluid, cell, tissue sample, biopsy, tissue print, skin, hair, a soluble fraction of a cell preparation, or media in which cells were grown. 
     
     
         16 . The method of  claim 15 , wherein the body fluid is blood, urine, plasma, saliva, or cerebrospinal fluid. 
     
     
         17 . The method of any one of the preceding claims wherein an immune response in the cancer that is lacking STING activity or cGAS activity is enhanced by administration of an oncolytic virus. 
     
     
         18 . The method of  claim 18 , wherein the immune response includes modulation of T cell activity, modulation of dendritic cell activity, or modulation of immune cytokines. 
     
     
         19 . The method of any one of the preceding claims, wherein the therapy results in increased tumor cell death and/or retarded tumor growth.