Diagnosis and treatment of cancer

Abstract

A method of diagnosing cancer in a human patient comprising the steps of (i) obtaining a sample containing nucleic acid and/or protein from the patient; and (ii) determining whether the sample contains a level of hNeNa voltage-gated Na + channel nucleic acid or protein associated with cancer. A method of treating cancer comprising the step of administering to the patient an agent which selectively prevents the function of hNe—Na voltage-gated Na + channel. A genetic construct comprising a nucleic acid encoding a molecule capable of preventing the function of hNeNa voltage-gated Na + channel expressed in a cell. The methods and compositions are particularly suited to prostate cancer.

1 - 54 . (canceled)  
     
     
         55 . A method of evaluating a condition of a human patient with respect to cancer comprising the steps of: 
 (a) obtaining a sample containing nucleic acid and/or protein from the patient; and    (b) determining whether the sample contains a level of hNe—Na voltage-gated Na+channel nucleic acid or protein associated with cancer;    (c) wherein said condition is selected from the group consisting of 
 (i) determining the susceptibility of a human patient to cancer,  
 (ii) diagnosing cancer in a human patient, and  
 (iii) predicting the relative prospects of a particular outcome of cancer in a human patient.  
   
     
     
         56 . A method according to  claim 55  wherein the cancer is prostate cancer.  
     
     
         57 . A method according to  claim 55  wherein the cancer is metastatic.  
     
     
         58 . A method according to any one of claims  55 - 57  wherein the sample contains nucleic acid and the level of hNe—Na voltage-gated Na +  channel nucleic acid is measured by contacting the said nucleic acid with a nucleic acid which hybridises selectively to hNe—Na voltage-gated Na +  channel nucleic acid.  
     
     
         59 . A method according to  claim 58  wherein the sample contains a mRNA and the nucleic acid as said selectively hybridises to hNe—Na voltage-gated Na +  channel mRNA.  
     
     
         60 . A method according to  claim 58  wherein the nucleic acid which hybridises as said is selected from the group consisting of those that are single stranded, are suitable for use in the nucleic acid amplification reaction, or a combination thereof and is detectably labeled.  
     
     
         61 . A method according to  claim 59  wherein the nucleic acid which hybridises as said is selected from the group consisting of those that are single stranded, are suitable for use in a nucleic acid amplification reaction, or a combination thereof and is detectably labeled.  
     
     
         62 . A method according to any one of claims  55 - 57  wherein the sample contains protein and the level of hNe—Na voltage-gated Na +  channel protein is measured.  
     
     
         63 . A method according to  claim 62  wherein the level of said protein is measured by contacting the protein with a molecule which selectively binds to hNe—Na voltage-gated Na +  channel protein.  
     
     
         64 . A method according to  claim 62  wherein the selective binding molecule is an antibody or fragment or derivative thereof or an antibody-like molecule.  
     
     
         65 . A method according to  claim 62  wherein the selective binding molecule comprises a detectable label.  
     
     
         66 . A method according to  claim 63  wherein the selective binding molecule comprises a detectable label.  
     
     
         67 . A method according to  claim 55  wherein the sample is a sample of the tissue in which cancer is suspected or in which cancer may be or has been found, or contains cells from said tissue.  
     
     
         68 . A method according to  claim 67  wherein the tissue is prostate and the cancer is prostate cancer.  
     
     
         69 . A method according to  claim 67  wherein the sample is any one of urine, semen, blood or lymphatic circulation and the cancer is prostate cancer.  
     
     
         70 . A method of manufacturing a reagent comprising the step of determining the level of hNe—Na voltage-gated Na +  channel protein or nucleic acid in a sample in the manufacture of a reagent for diagnosing cancer using an agent selected from the group consisting of a nucleic acid which selectively hybridises to hNe—Na voltage-gated Na +  channel nucleic acid and a molecule which selectively binds to hNe—Na voltage-gated Na +  channel protein.  
     
     
         71 . A method as in  claim 70  wherein an agent as defined therein is used in a method of diagnosing cancer.  
     
     
         72 . A method as in  claim 70  wherein an agent as defined therein is used for diagnosing cancer.  
     
     
         73 . A kit of parts useful for diagnosing cancer comprising an agent s which is capable of use in determining the level of hNe—Na VGSC protein or nucleic acid in a sample.  
     
     
         74 . A kit of parts according to  claim 73  further comprising a control selected from the group consisting of negative controls, positive controls and combinations thereof.  
     
     
         75 . A kit of parts according to any one of claims  73  or  74  further comprising means for separating prostatic epithelial cells from a sample.  
     
     
         76 . A method of treating cancer comprising the step of administering to the patient an agent which selectively prevents the function of hNe—Na voltage-gated Na +  channel.  
     
     
         77 . A method according to  claim 76  wherein the agent prevents the expression of hNe—Na voltage-gated Na +  channel.  
     
     
         78 . A method according to  claim 76  wherein the agent inhibits the activity of hNe—Na voltage-gated Na +  channel.  
     
     
         79 . A method according to  claim 77  wherein the agent is an antisense molecule.  
     
     
         80 . A method according to  claim 77  wherein the agent is a ribozyme.  
     
     
         81 . A method of manufacturing a medicament for treating cancer comprising the step of using an agent which selectively prevents the function of hNe—Na voltage-gated Na +  channel.  
     
     
         82 . A genetic construct comprising a nucleic acid encoding a molecule capable of preventing the function of hNe—Na voltage-gated Na +  channel expressed in a cell.  
     
     
         83 . A genetic construct according to  claim 82  adapted for delivery to a human cell.  
     
     
         84 . A genetic construct according to  claim 83  wherein the adaptation allows delivery to a cancer cell.  
     
     
         85 . A genetic construct according to  claim 84  comprising means to selectively deliver the nucleic acid to a cancer cell.  
     
     
         86 . A genetic construct according to any one of  claims 82  to  85  comprising means to selectively express the nucleic acid encoding a molecule as said in a cancer cell.  
     
     
         87 . A genetic construct according to any one of  claims 82  to  85  for use in medicine.  
     
     
         88 . A genetic construction according to any one of  claims 82  to  85  further comprising in combination a pharmaceutically acceptable carrier wherein said genetic compound is used in a pharmaceutical composition.  
     
     
         89 . A method of identifying a compound which selectively inhibits a hNe—Na voltage-gated Na +  channel, the method comprising 
 (a) contacting a test compound with any one of the said voltage-gated Na +  channels and determining whether said compound is inhibitory;    (b) contacting the test compound with other voltage-gated Na +  channels and determining whether said compound is inhibitory; and    (c) selecting a compound which is substantially inhibitory in (a) but is not substantially inhibitory in (b).    
     
     
         90 . A compound comprising a moiety which selectively binds hNe—Na voltage-gated Na +  channel protein and a further moiety.  
     
     
         91 . A compound according to  claim 90  wherein the further moiety is a directly or indirectly cytotoxic moiety.  
     
     
         92 . A compound according to  claim 90  wherein the further moiety is a readily detectable moiety.  
     
     
         93 . A compound according to  claim 90  wherein the moiety which selectively binds hNe—Na voltage-gated Na +  channel protein and the further moiety are polypeptides which are fused.  
     
     
         94 . A compound according to  claim 93  wherein said compound is encoded in a nucleic acid molecule.  
     
     
         95 . A compound molecule according to  claim 94  wherein said nucleic acid is included in a host cell.  
     
     
         96 . A compound according to any one of  claims 90  to  93  wherein said compound is for use in medicine.  
     
     
         97 . A compound according to any one of  claims 90  to  93  in combination with a pharmaceutically acceptable carrier in a pharmaceutical composition.  
     
     
         98 . A compound according to any one of  claims 90  to  93  wherein said compound is used in the manufacture of a medicament for the treatment and/or diagnosis of a human patient with or at risk of cancer.  
     
     
         99 . A method of treating cancer, the method comprising the step of administering to the human patient an effective amount of a compound according to any one of claims  90 ,  91  or  93  wherein the further moiety of the compound is one which either directly or indirectly is of therapeutic benefit to the patient.  
     
     
         100 . A method of imaging cancer in a human patient, comprising administering to the patient an effective amount of a compound according to  claim 92.