Compositions and Methods for Diagnosing and Treating Cancer

Abstract

The present invention relates to compositions and methods for characterizing, diagnosing, and treating cancer. In particular the invention provides the means and methods for the diagnosis, characterization, prognosis and treatment of cancer and specifically targeting cancer stem cells. The present invention provides a soluble FZD receptor comprising an extracellular domain of a human FZD receptor that inhibits growth of tumor cells. The present invention still further provides a soluble receptor comprising a Fri domain of a human FZD receptor that binds a ligand of a human FZD receptor and said soluble receptor is capable of inhibiting tumor growth. The present invention still further provides a method of treating cancer comprising administering a soluble FZD receptor comprising for example, either an extracellular domain of a human FZD receptor or a Fri domain of a human FZD receptor, in an amount effective to inhibit tumor growth.

1 - 41 . (canceled) 
     
     
         42 . A soluble receptor comprising
 (a) a fragment of an extracellular domain of a human Frizzled (FZD) receptor, wherein the fragment comprises the Fri domain of the human FZD receptor, and   (b) a human Fc domain.   
     
     
         43 . A polynucleotide encoding the soluble receptor of  claim 42 . 
     
     
         44 . A method of treating cancer in a subject in need thereof comprising administering to the subject an effective amount of the soluble receptor of  claim 42 . 
     
     
         45 . A kit comprising a soluble receptor, wherein the soluble receptor comprises
 (a) a fragment of an extracellular domain of a human Frizzled (FZD) receptor, wherein the fragment comprises the Fri domain of the human FZD receptor, and   (b) a human Fc domain.   
     
     
         46 . The kit of  claim 45 , wherein the soluble receptor
 (a) has a longer half-life in vivo than a soluble receptor comprising the extracellular domain of the human FZD receptor and the human Fc domain;   (b) has a half-life in vivo of at least 24 hours in mice following i.p. injection; or   (c) is detectable in serum at least 24 hours following i.p. injection in mice.   
     
     
         47 . The kit of  claim 45 , wherein the fragment of an extracellular domain of a human FZD receptor consists of the Fri domain of the human FZD receptor. 
     
     
         48 . The kit of  claim 45 , wherein the fragment of an extracellular domain of a human FZD receptor consists of the Fri domain of the human FZD receptor, and the fragment is fused to the human Fc domain. 
     
     
         49 . A kit comprising a soluble receptor comprising the mature form of a polypeptide, wherein the polypeptide
 (a) comprises (i) a first polypeptide having at least 95% sequence identity to SEQ ID NO:7, SEQ ID NO:8, or SEQ ID NO:9 and (ii) a second polypeptide which is a non-FZD receptor protein sequence comprising (1) a human Fc domain or (2) a polypeptide having the amino acid sequence of SEQ ID NO:4, wherein the first polypeptide is capable of binding a ligand of a human FZD receptor and is fused to the second polypeptide; or   (b) consists of the first and second polypeptides.   
     
     
         50 . The kit of  claim 45 , wherein the human FZD receptor comprises FZD4, FZD5, or FZD8. 
     
     
         51 . The kit of  claim 50 , wherein the Fri domain comprises the amino acids from approximately 28 to 158 of SEQ ID NO:7, the amino acids from approximately 37 to 170 of SEQ ID NO:8, or the amino acids from approximately 27 to 157 of SEQ ID NO:9. 
     
     
         52 . The kit of  claim 51 , wherein Fri domain consists of the amino acids 28 to 158 of SEQ ID NO:7, the amino acids 37 to 170 of SEQ ID NO:8, or the amino acids 27 to 157 of SEQ ID NO:9. 
     
     
         53 . The kit of  claim 46 , wherein the human FZD receptor comprises FZD4, FZD5, or FZD8. 
     
     
         54 . The kit of  claim 53 , wherein the Fri domain comprises the amino acids from approximately 28 to 158 of SEQ ID NO:7, the amino acids from approximately 37 to 170 of SEQ ID NO:8, or the amino acids from approximately 27 to 157 of SEQ ID NO:9. 
     
     
         55 . The kit of  claim 54 , wherein Fri domain consists of the amino acids 28 to 158 of SEQ ID NO:7, the amino acids 37 to 170 of SEQ ID NO:8, or the amino acids 27 to 157 of SEQ ID NO:9. 
     
     
         56 . The kit of  claim 47 , wherein the human FZD receptor comprises FZD4, FZD5, or FZD8. 
     
     
         57 . The kit of  claim 56 , wherein the Fri domain comprises the amino acids from approximately 28 to 158 of SEQ ID NO:7, the amino acids from approximately 37 to 170 of SEQ ID NO:8, or the amino acids from approximately 27 to 157 of SEQ ID NO:9. 
     
     
         58 . The kit of  claim 57 , wherein Fri domain consists of the amino acids 28 to 158 of SEQ ID NO:7, the amino acids 37 to 170 of SEQ ID NO:8, or the amino acids 27 to 157 of SEQ ID NO:9. 
     
     
         59 . The kit of  claim 48 , wherein the human FZD receptor comprises FZD4, FZD5, or FZD8. 
     
     
         60 . The kit of  claim 59 , wherein the Fri domain comprises the amino acids from approximately 28 to 158 of SEQ ID NO:7, the amino acids from approximately 37 to 170 of SEQ ID NO:8, or the amino acids from approximately 27 to 157 of SEQ ID NO:9. 
     
     
         61 . The kit of  claim 60 , wherein Fri domain consists of the amino acids 28 to 158 of SEQ ID NO:7, the amino acids 37 to 170 of SEQ ID NO:8, or the amino acids 27 to 157 of SEQ ID NO:9.