Therapeutic and diagnostic methods relating to cancer stem cells

Abstract

Genes that are deregulated in cancer stem cells (e.g., melanoma stem cells) are disclosed. Methods which involve modulating (e.g., inducing, inhibiting, etc.) the activity of the cancer stem cell associated genes are used to treat individuals having melanoma. Cell surface genes that are upregulated in melanoma stem cells are targeted for the selective isolation, detection, and killing of cancer stem cells in melanoma.

1 . A method for diagnosing cancer in an individual, comprising:
 determining an expression level of a cancer stem cell (CSC)-associated gene in Table 5 in a test sample from the individual; and   comparing the expression level of the CSC-associated gene to a reference value, wherein results of the comparison are diagnostic of cancer.   
     
     
         2 . The method of  claim 1 , wherein the cancer is melanoma, breast cancer, prostate cancer, colon cancer or lung cancer. 
     
     
         3 . (canceled) 
     
     
         4 . The method of  claim 1 , wherein the determining comprises detecting in the test sample a mRNA that is encoded by the CSC-associated gene. 
     
     
         5 . The method of  claim 1 , wherein the determining comprises detecting in the test sample a polypeptide that is encoded by the CSC-associated gene. 
     
     
         6 - 12 . (canceled) 
     
     
         13 . The method of  claim 1 , wherein the reference value is the expression level of the CSC-associated gene in a non-cancer reference sample, and wherein, if the expression level of the CSC-associated gene in the test sample is about equal to the expression level of the CSC-associated gene in the non-cancer reference sample, then the comparison does not indicate cancer. 
     
     
         14 . The method of  claim 1 , wherein the reference value is the expression level of the CSC-associated gene in a cancer reference sample, and wherein, if the expression level of the CSC-associated gene is about equal to the expression level of the CSC-associated gene in the cancer reference sample, then the comparison indicates cancer. 
     
     
         15 . The method of  claim 1 , wherein the CSC-associated gene is in Table 1 or 8, wherein the reference value is the expression level of the CSC-associated gene in a non-cancer reference sample, and wherein, if the expression level of the CSC-associated gene in the test sample is significantly higher than the expression level of the CSC-associated gene in the non-cancer reference sample, the comparison indicates cancer. 
     
     
         16 - 17 . (canceled) 
     
     
         18 . The method of  claim 1 , wherein the CSC-associated gene is in Table 2 or 7, wherein the reference value is the expression level of the CSC-associated gene in a non-cancer reference sample, and wherein, if the expression level of the CSC-associated gene in the test sample is significantly lower than the expression level of the CSC-associated gene in the non-cancer reference sample, the comparison indicates cancer. 
     
     
         19 - 42 . (canceled) 
     
     
         43 . A method for treating an individual having, or at risk of having, cancer, comprising:
 administering a therapeutically effective amount of a composition that targets a product of a CSC-associated gene selected from the group set forth in Table 1 or 8.   
     
     
         44 . The method of  claim 43 , wherein the cancer is melanoma, breast cancer, prostate cancer, colon cancer or lung cancer. 
     
     
         45 . The method of  claim 43 , wherein the CSC-associated gene is selected from the group set forth in Table 4. 
     
     
         46 . The method of  claim 45 , wherein the CSC-associated gene is selected from the group consisting of: ANK2, NCKAP1L, PTPRE, PTPRS, SBF1, SCN3A, SGCA, SGCB, SLC2A11, SLC2A8, SLC4A1, STX3, and TBC1D8. 
     
     
         47 . The method of  claim 43 , wherein the composition comprises a small interfering nucleic acid that inhibits expression of the CSC-associated gene. 
     
     
         48 - 51 . (canceled) 
     
     
         52 . The method of  claim 45 , wherein the composition comprises an isolated molecule that selectively binds to a polypeptide encoded by the CSC-associated gene. 
     
     
         53 . The method of  claim 52 , wherein the isolated molecule is conjugated to a therapeutic agent. 
     
     
         54 . The method of  claim 53 , wherein the isolated molecule is an antibody or antigen-binding fragment. 
     
     
         55 - 65 . (canceled) 
     
     
         66 . A method of delivering a therapeutic agent to a cancer stem cell, comprising:
 contacting a cancer stem cell with an isolated molecule that selectively binds to a polypeptide encoded by a CSC-associated gene selected from the group set forth in Table 4 conjugated to a therapeutic agent in an effective amount to deliver the therapeutic agent to the cancer stem cell.   
     
     
         67 . The method of  claim 66 , wherein the CSC-associated gene is selected from the 5 group consisting of: ANK2, NCKAP1L, PTPRE, PTPRS, SBF1, SCN3A, SGCA, SGCB, SLC2A11, SLC2A8, SLC4A1, STX3, and TBC1D8. 
     
     
         68 . (canceled) 
     
     
         69 . The method of  claim 66 , wherein the therapeutic agent is selected from: a toxin, a small-interfering nucleic acid, and a chemotherapeutic agent. 
     
     
         70 - 71 . (canceled) 
     
     
         72 . A nucleic acid array consisting essentially of at least 2, at least 5, at least 10, at least 20, at least 50, at least 100, at least 200, at least 300, or more CSC-associated genes set forth in Table 5. 
     
     
         73 - 84 . (canceled)