Methods and assays relating to circulating tumor cells

Abstract

The technology described herein relates to methods of detecting circulating tumor cells (CTCs), e.g. by detecting changes in the expression of certain CTC marker genes. Aberrant expression of CTC marker genes, e.g. changes in expression indicative of CTCs can also be targeted in order to treat cancer.

What is claimed herein is: 
     
         1 . A method of detecting circulating tumor cells (CTCs) in a sample, the method comprising:
 measuring the level of a PC-CTC marker gene expression product in the sample;   wherein a level of the marker gene expression product which is greater than a reference level indicates the presence of CTCs in the sample.   
     
     
         2 . The method of  claim 1 , wherein the CTCs are pancreatic cancer CTCs. 
     
     
         3 . The method of  claim 1 , wherein the method further comprises a first step of isolating the CTCs from the sample. 
     
     
         4 . The method of  claim 1 , wherein the expression product is a nucleic acid or a polypeptide. 
     
     
         5 . The method of  claim 1 , wherein the CTC marker gene is selected from Table 7; Table 8; or
 Table 14.   
     
     
         6 . The method of  claim 1 , wherein the CTC marker gene is selected from the group consisting of:
 ABI3BP; ADAMTS5; ADAMTSL1; ANG; ARSA; C1RL; C3; C4A; C4B; CCDC80; CD109; CHI3L1; CLEC3B; CMTM3; CMTM7; COL14A1; COL1A2; COL3A1; COL4A6; CSF1; DAG1; DCN; DMKN; FBLN1; FGF1; FMOD; GPC3; GPC4; HMGB1; IFNAR2; IGFBP5; IL16; LAMA4; LTBP4; MFAP1A; NID2; OGN; PDAP1; PF4; PLAT; PODN; PRELP; RSPO1; SERPING1; SLURP1; SOD3; SPARC; SPOCK2; SPON2; SULF1; SULF2; TGFB2; TGM2; THBD; THBS1; THSD4; TIMP2; TNXB; TPT1; TWSG1 and WNT4.   
     
     
         7 . The method of  claim 1 , wherein the CTC marker gene is selected from the group consisting of:
 ALDH1A1; ALDH1A2; IGFBP5; KLF4; DCN; SPARC; WNT; TGFB2; VEGF; COL1A2; COL3A1; and TIMP2.   
     
     
         8 . The method of  claim 1 , wherein the CTC marker gene is selected from the group consisting of:
 ALDH1A2; IGFBP5; KLF4; DCN; and SPARC.   
     
     
         9 . The method of  claim 1 , wherein the CTC marker gene is selected from the group consisting of:
 ALDH1A2; IGFBP5; KLF4; and DCN.   
     
     
         10 . The method of  claim 1 , wherein the CTC marker gene is selected from the group consisting of:
 TPT1; HMGB1; SPON 2; SPARC; and ARSA.   
     
     
         11 . The method of  claim 1 , wherein the CTC marker gene is selected from the group consisting of:
 IL6ST; ARSA; TIMP2; CD55; SULF2; ITGA6; SDC4; CDON; and SV2A.   
     
     
         12 . A method of treating cancer in a subject, the method comprising administering a therapeutically effective amount of a CTC marker gene-targeted therapy to the subject. 
     
     
         13 . The method of  claim 12 , wherein the cancer is pancreatic cancer. 
     
     
         14 . The method of  claim 12 , wherein the CTC marker gene-targeted therapy comprises an inhibitor of a CTC marker gene. 
     
     
         15 . The method of  claim 14 , wherein the inhibitor is an antibody reagent. 
     
     
         16 . The method of  claim 14 , wherein the inhibitor is an inhibitory nucleic acid reagent. 
     
     
         17 . The method of  claim 12 , wherein the CTC marker gene-targeted therapy comprises a CTC marker gene-binding antibody reagent and a chemotherapeutic agent. 
     
     
         18 . The method of  claim 15 , wherein the subject is a subject determined to have an elevated level of CTCs and/or an elevated level of a CTC marker gene present in the blood and/or stroma of the cancer. 
     
     
         19 . The method of  claim 15 , wherein the CTC marker gene-targeted therapy comprises a CTC marker gene-binding antibody reagent that binds a marker gene selected from the group consisting of:
 IL6ST, SULF2, and SV2A.   
     
     
         20 . A method of determining if a subject is likely to respond to treatment with a CTC marker gene-targeted therapy, the method comprising:
 measuring the level of a CTC marker gene expression product present in the blood and/or stroma of a cancer; and   determining that the subject is likely to respond to the treatment if the level of the expression product is increased relative to a reference level.