US2006134661A1PendingUtilityA1

Treatment of cancer and compositions

Assignee: ESSNER RICHARDPriority: Oct 12, 2004Filed: Oct 12, 2005Published: Jun 22, 2006
Est. expiryOct 12, 2024(expired)· nominal 20-yr term from priority
Inventors:Richard Essner
C12Q 2600/106C12Q 2600/112A61P 35/00C12Q 2600/118C12Q 2600/136C12Q 2600/158C07K 14/4748C12Q 1/6886
43
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Claims

Abstract

The invention discloses a method of identifying a gene associated with stage III primary cancer or lymph node metastasis. The genes so identified include CAV1, CST3, LIMK1, MMP2, MMP15, VEGF, ETV4, MMP9, PIK3C2B, and SERPIN1. Also disclosed are methods for diagnosis, prognosis, and treatment of cancer. The invention further discloses compositions for preventing and treating diseases.

Claims

exact text as granted — not AI-modified
1 . A method of identifying a gene associated with stage III primary cancer or lymph node metastasis, comprising: 
 identifying a metastasis-associated gene differentially expressed in stage I or II primary cancer than in stage III primary cancer;    analyzing the expression of the gene in the stage I or II primary cancer and the stage III primary cancer or lymph node metastasis; and    relating the expression of the gene to the stage III primary cancer, the lymph node metastasis, or a combination thereof.    
     
     
         2 . The method of  claim 1 , wherein the cancer is melanoma, breast cancer, colon cancer, lung cancer, or merkel cell carinoma.  
     
     
         3 . A method of determining whether a subject is likely to be suffering from stage III cancer, comprising: 
 providing a test sample from a subject; and    detecting the expression of one or more genes selected from a first group consisting of CAV1, CST3, LIMK1, MMP2, MMP15, VEGF, ETV4, MMP9, PIK3C2B, and SERPIN1 in the sample,    wherein the expression of one or more genes selected from a second group consisting of CAV1, CST3, LIMK1, MMP2, MMP15, and VEGF in the sample, if higher than its respective control value, the expression of one or more genes selected from a third group consisting of ETV4, MMP9, PIK3C2B, and SERPIN1 in the sample, if lower than its respective control value, or a combination thereof, indicates that the subject is likely to be suffering from stage III cancer.    
     
     
         4 . The method of  claim 3 , wherein the cancer is melanoma, breast cancer, colon cancer, lung cancer, or merkel cell carinoma.  
     
     
         5 . The method of  claim 3 , wherein the sample is a freshly prepared primary tumor sample, a frozen primary tumor sample, a paraffin-embedded primary tumor sample, or a blood sample.  
     
     
         6 . The method of  claim 3 , wherein the control value is the expression level of the gene in a stage I or II primary tumor sample.  
     
     
         7 . A method of staging cancer, comprising: 
 providing a test sample from a subject; and    detecting the expression of one or more genes selected from a first group consisting of CAV1, LIMK1, MMP15, and VEGF in the sample,    wherein the level of the expression of the one or more genes indicates that the subject is likely to be suffering from stage I or II primary cancer, stage III primary cancer with micrometastasis, stage III primary cancer with macrometastasis, or lymph node metastasis.    
     
     
         8 . The method of  claim 7 , wherein the cancer is melanoma, breast cancer, colon cancer, lung cancer, or merkel cell carinoma.  
     
     
         9 . The method of  claim 7 , wherein the sample is a freshly prepared primary tumor sample, a frozen primary tumor sample, a paraffin-embedded primary tumor sample, or a blood sample.  
     
     
         10 . The method of  claim 7 , wherein the one or more genes are selected from a second group consisting of CAV1, LIMK1, and VEGF, wherein the level of the expression of the one or more genes indicates that the subject is likely to be suffering from stage III primary cancer with micrometastasis or stage III primary cancer with macrometastasis.  
     
     
         11 . The method of  claim 7 , wherein the one or more genes are selected from a third group consisting of LIMK1 and VEGF.  
     
     
         12 . A method of identifying a candidate compound for treating stage III cancer, comprising: 
 providing a stage III cancer cell that expresses one or more genes selected from a first group consisting of CAV1, CST3, LIMK1, MMP2, MMP15, VEGF, ETV4, MMP9, PIK3C2B, and SERPIN1;    contacting the cell with a test compound; and    detecting the expression of the one or more genes selected from the first group in the cell,    wherein the expression of one or more genes selected from a second group consisting of CAV1, CST3, LIMK1, MMP2, MMP15, and VEGF, if lower than its respective control value, the expression of one or more genes selected from a third group consisting of ETV4, MMP9, PIK3C2B, and SERPIN1, if higher than its respective control value, or a combination thereof, indicates that the test compound is a candidate for treating stage III cancer.    
     
     
         13 . The method of  claim 12 , wherein the cancer is melanoma, breast cancer, colon cancer, lung cancer, or merkel cell carinoma.  
     
     
         14 . A method of identifying a candidate compound for treating cancer, comprising: 
 providing a system that expresses one or more genes selected from a first group consisting of CAV1, CST3, MMP15, ETV4, MMP9, PIK3C2B, and SERPIN1;    contacting the system with a test compound; and    detecting the expression of the one or more genes selected from the first group in the system,    wherein the expression of one or more genes selected from a second group consisting of CAV1, CST3, and MMP15, if lower than its respective control value, the expression of one or more genes selected from a third group consisting of ETV4, MMP9, PIK3C2B, and SERPIN1, if higher than its respective control value, or a combination thereof, indicates that the test compound is a candidate for treating cancer.    
     
     
         15 . The method of  claim 14 , wherein the cancer is melanoma, breast cancer, colon cancer, lung cancer, or merkel cell carinoma.  
     
     
         16 . A method of treating stage III cancer, comprising: 
 identifying a subject suffering from stage III cancer; and    administering to the subject one or more compounds that decrease the expression of one or more genes selected from a first group consisting of CAV1, CST3, LIMK1, MMP2, MMP15, and VEGF, increase the expression of one or more genes selected from a second group consisting of ETV4, MMP9, PIK3C2B, and SERPIN1, or a combination thereof, in the subject.    
     
     
         17 . The method of  claim 16 , wherein the cancer is melanoma, breast cancer, colon cancer, lung cancer, or merkel cell carinoma.  
     
     
         18 . The method of  claim 16 , wherein the one or more compounds are administered topically.  
     
     
         19 . The method of  claim 18 , wherein the one or more compounds are administered with a transdermal drug delivery agent.  
     
     
         20 . The method of  claim 19 , wherein the one or more compounds are admixed with a lotion, cream, emulsion, oil, liquid, or gel, or embedded in a patch.  
     
     
         21 . The method of  claim 20 , wherein the one or more compounds are admixed with a sunscreen cream.  
     
     
         22 . The method of  claim 16 , wherein the one or more compounds are siRNAs, ribozymes, antisense nucleotides, transcription factor decoys, small molecules, or a combination thereof.  
     
     
         23 . The method of  claim 22 , wherein the one or more compounds include an siRNA targeting  
       
         
           
                 
                 
                 
               
                     
                 
                   LIMK1 mRNA at 
                     
                     
                 
                   CCGCUACUGCCCCCCAAACUG, 
                   (SEQ ID NO:1) 
                 
                     
                 
                   CUGGCCGGCCACCUGCCACUG, 
                   (SEQ ID NO:2) 
                 
                     
                 
                   ACCGCUACUGCCCCCCAAACU, 
                   (SEQ ID NO:3) 
                 
                     
                 
                   CUGGCUCCCACCUGCCCCACA, 
                   (SEQ ID NO:4) 
                 
                     
                 
                   CCGAGACCUCAACUCCCACAA, 
                   (SEQ ID NO:5) 
                 
                     
                 
                   GGACCGCUACUGCCCCCCAAA, 
                   (SEQ ID NO:6) 
                 
                     
                 
                   CCGGCGCGGCGAGAGCGGACU, 
                   (SEQ ID NO:7) 
                 
                     
                 
                   GAGACCUCAACUCCCACAACU, 
                   (SEQ ID NO:8) 
                 
                     
                 
                   CUGCCCCCCGAGCUUCUUCCC, 
                   (SEQ ID NO:9) 
                 
                     
                 
                   UGGGUGCUCUGAGCAAAUCAC, 
                   (SEQ ID NO:10) 
                 
                   or 
                 
                     
                 
                   GGGCAGCUCUGCCCGGCAGAA, 
                   (SEQ ID NO:11) 
                 
                     
                 
                   an siRNA targeting dLIMK1 mRNA at 
                 
                   CAGCCGCCUGCUCCAGCUGAC, 
                   (SEQ ID NO:12) 
                 
                     
                 
                   CCAUGGGUGCUCUGAGCAAAU, 
                   (SEQ ID NO:13) 
                 
                     
                 
                   CAUGGGUGCUCUGAGCAAAUC, 
                   (SEQ ID NO:14) 
                 
                     
                 
                   AUGGGUGCUCUGAGCAAAUCA, 
                   (SEQ ID NO:15) 
                 
                     
                 
                   ACGGCCCACCGGGCUGUGGCA, 
                   (SEQ ID NO:16) 
                 
                     
                 
                   GUGGCACCGAGCACUCACACA, 
                   (SEQ ID NO:17) 
                 
                     
                 
                   AUGGCACGCCCAUCCGAAAUG, 
                   (SEQ ID NO:18) 
                 
                     
                 
                   UGGCACGCCCAUCCGAAAUGU, 
                   (SEQ ID NO:19) 
                 
                     
                 
                   CUGCCUCACGUGUGGGACCUU, 
                   (SEQ ID NO:20) 
                 
                     
                 
                   UCCCUGUCGCACCAGUACUAU, 
                   (SEQ ID NO:21) 
                 
                     
                 
                   CCCUGAGCUCUCCGGCUUAUA, 
                   (SEQ ID NO:22) 
                 
                   or 
                 
                     
                 
                   GCCUCACGUGUGGGACCUUUA, 
                   (SEQ ID NO:23) 
                 
                     
                 
                   an siRNA targeting VEGF mRNA at 
                 
                   GCGCAGCUACUGCCAUCCAAU, 
                   (SEQ ID NO:24) 
                 
                     
                 
                   CAGCGCAGCUACUGCCAUCCA, 
                   (SEQ ID NO:25) 
                 
                     
                 
                   UUGGAGCCUUGCCUUGCUGCU, 
                   (SEQ ID NO:26) 
                 
                     
                 
                   CAGGCUGCACCCAUGGCAGAA, 
                   (SEQ ID NO:27) 
                 
                     
                 
                   GUGGGCCUUGCUCAGAGCGGA, 
                   (SEQ ID NO:28) 
                 
                     
                 
                   AGGCGAGGCAGCUUGAGUUAA, 
                   (SEQ ID NO:29) 
                 
                     
                 
                   GGCGAGGCAGCUUGAGUUAAA, 
                   (SEQ ID NO:30) 
                 
                     
                 
                   UUGCUCAGAGCGGAGAAAGCA, 
                   (SEQ ID NO:31) 
                 
                     
                 
                   UGCCCACUGAGGAGUCCAACA, 
                   (SEQ ID NO:32) 
                 
                   or 
                 
                     
                 
                   GCCCACUGAGGAGUCCAACAU, 
                   (SEQ ID NO:33) 
                 
                   or 
                 
                     
                 
                   a combination thereof. 
                 
                     
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         24 . A method of treating cancer, comprising: 
 identifying a subject suffering from cancer as staged using the method of  claim 7;  and    administering to the subject one or more compounds that decrease the expression of one or more genes selected from a first group consisting of CAV1, CST3, LIMK1, MMP2, MMP15, and VEGF, increase the expression of one or more genes selected from a second group consisting of ETV4, MMP9, PIK3C2B, and SERPIN1, or a combination thereof, in the subject.    
     
     
         25 . The method of  claim 24 , wherein the cancer is melanoma, breast cancer, colon cancer, lung cancer, or merkel cell carinoma.  
     
     
         26 . The method of  claim 24 , wherein the one or more compounds are administered topically.  
     
     
         27 . The method of  claim 26 , wherein the one or more compounds are administered with a transdermal drug delivery agent  
     
     
         28 . The method of  claim 27 , wherein the one or more compounds are admixed with a lotion, cream, emulsion, oil, liquid, or gel, or embedded in a patch.  
     
     
         29 . The method of  claim 28 , wherein the one or more compounds are admixed with a sunscreen cream.  
     
     
         30 . The method of  claim 25 , wherein the one or more compounds are siRNAs, ribozymes, antisense nucleotides, transcription factor decoys, small molecules, or a combination thereof.  
     
     
         31 . The method of  claim 30 , wherein the one or more compounds include an siRNA targeting  
       
         
           
                 
                 
                 
               
                     
                 
                   LIMK1 mRNA at 
                     
                     
                 
                   CCGCUACUGCCCCCCAAACUG, 
                   (SEQ ID NO:1) 
                 
                     
                 
                   CUGGCCGGCCACCUGCCACUG, 
                   (SEQ ID NO:2) 
                 
                     
                 
                   ACCGCUACUGCCCCCCAAACU, 
                   (SEQ ID NO:3) 
                 
                     
                 
                   CUGGCUCCCACCUGCCCCACA, 
                   (SEQ ID NO:4) 
                 
                     
                 
                   CCGAGACCUCAACUCCCACAA, 
                   (SEQ ID NO:5) 
                 
                     
                 
                   GGACCGCUACUGCCCCCCAAA, 
                   (SEQ ID NO:6) 
                 
                     
                 
                   CCGGCGCGGCGAGAGCGGACU, 
                   (SEQ ID NO:7) 
                 
                     
                 
                   GAGACCUCAACUCCCACAACU, 
                   (SEQ ID NO:8) 
                 
                     
                 
                   CUGCCCCCCGAGCUUCUUCCC, 
                   (SEQ ID NO:9) 
                 
                     
                 
                   UGGGUGCUCUGAGCAAAUCAC, 
                   (SEQ ID NO:10) 
                 
                   or 
                 
                     
                 
                   GGGCAGCUCUGCCCGGCAGAA, 
                   (SEQ ID NO:11) 
                 
                     
                 
                   an siRNA targeting dLIMK1 mRNA at 
                 
                   CAGCCGCCUGCUCCAGCUGAC, 
                   (SEQ ID NO:12) 
                 
                     
                 
                   CCAUGGGUGCUCUGAGCAAAU, 
                   (SEQ ID NO:13) 
                 
                     
                 
                   CAUGGGUGCUCUGAGCAAAUC, 
                   (SEQ ID NO:14) 
                 
                     
                 
                   AUGGGUGCUCUGAGCAAAUCA, 
                   (SEQ ID NO:15) 
                 
                     
                 
                   ACGGCCCACCGGGCUGUGGCA, 
                   (SEQ ID NO:16) 
                 
                     
                 
                   GUGGCACCGAGCACUCACACA, 
                   (SEQ ID NO:17) 
                 
                     
                 
                   AUGGCACGCCCAUCCGAAAUG, 
                   (SEQ ID NO:18) 
                 
                     
                 
                   UGGCACGCCCAUCCGAAAUGU, 
                   (SEQ ID NO:19) 
                 
                     
                 
                   CUGCCUCACGUGUGGGACCUU, 
                   (SEQ ID NO:20) 
                 
                     
                 
                   UCCCUGUCGCACCAGUACUAU, 
                   (SEQ ID NO:21) 
                 
                     
                 
                   CCCUGAGCUCUCCGGCUUAUA, 
                   (SEQ ID NO:22) 
                 
                   or 
                 
                     
                 
                   GCCUCACGUGUGGGACCUUUA, 
                   (SEQ ID NO:23) 
                 
                     
                 
                   an siRNA targeting VEGF mRNA at 
                 
                   GCGCAGCUACUGCCAUCCAAU, 
                   (SEQ ID NO:24) 
                 
                     
                 
                   CAGCGCAGCUACUGCCAUCCA, 
                   (SEQ ID NO:25) 
                 
                     
                 
                   UUGGAGCCUUGCCUUGCUGCU, 
                   (SEQ ID NO:26) 
                 
                     
                 
                   CAGGCUGCACCCAUGGCAGAA, 
                   (SEQ ID NO:27) 
                 
                     
                 
                   GUGGGCCUUGCUCAGAGCGGA, 
                   (SEQ ID NO:28) 
                 
                     
                 
                   AGGCGAGGCAGCUUGAGUUAA, 
                   (SEQ ID NO:29) 
                 
                     
                 
                   GGCGAGGCAGCUUGAGUUAAA, 
                   (SEQ ID NO:30) 
                 
                     
                 
                   UUGCUCAGAGCGGAGAAAGCA, 
                   (SEQ ID NO:31) 
                 
                     
                 
                   UGCCCACUGAGGAGUCCAACA, 
                   (SEQ ID NO:32) 
                 
                   or 
                 
                     
                 
                   GCCCACUGAGGAGUCCAACAU, 
                   (SEQ ID NO:33) 
                 
                   or 
                 
                     
                 
                   a combination thereof. 
                 
                     
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         32 . A method of treating cancer, comprising: 
 identifying a subject suffering from cancer; and    administering to the subject one or more compounds selected from a group consisting of a first compound that inhibits the expression of CAV1, a second compound that inhibits the expression of CST3, a third compound that inhibits the expression of MMP15, a fourth compound that enhances the expression of ETV4, a fifth compound that enhances the expression of MMP9, a sixth compound that enhances the expression of PIK3C2B, and a seventh compound that enhances the expression of SERPIN1.    
     
     
         33 . The method of  claim 32 , wherein the cancer is melanoma, breast cancer, colon cancer, lung cancer, or merkel cell carinoma.  
     
     
         34 . The method of  claim 32 , wherein the one or more compounds are administered topically.  
     
     
         35 . The method of  claim 34 , wherein the one or more compounds are administered with a transdermal drug delivery agent.  
     
     
         36 . The method of  claim 35 , wherein the one or more compounds are admixed with a lotion, cream, emulsion, oil, liquid, or gel, or embedded in a patch.  
     
     
         37 . The method of  claim 36 , wherein the one or more compounds are admixed with a sunscreen cream.  
     
     
         38 . The method of  claim 33 , wherein the one or more compounds are siRNAs, ribozymes, antisense nucleotides, transcription factor decoys, or small molecules.  
     
     
         39 . A method of treating cancer, comprising: 
 identifying a subject suffering from cancer; and    administering to the subject a combination of at least two compounds selected from the group consisting of a first compound that inhibits the expression of CAV1, a second compound that inhibits the expression of CST3, a third compound that inhibits the expression of LIMK1, a fourth compound that inhibits the expression of MMP2, a fifth compound that inhibits the expression of MMP15, a sixth compound that inhibits the expression of VEGF, a seventh compound that enhances the expression of ETV4, an eighth compound that enhances the expression of MMP9, a ninth compound that enhances the expression of PIK3C2B, and a tenth compound that enhances the expression of SERPIN1,    wherein the combination is not a first combination of the third and fourth compounds, a second combination of the third and sixth compounds, a third combination of the fourth and sixth compounds, or a fourth combination of the third, fourth, and sixth compounds.    
     
     
         40 . The method of  claim 39 , wherein the cancer is melanoma, breast cancer, colon cancer, lung cancer, or merkel cell carinoma.  
     
     
         41 . The method of  claim 39 , wherein the compounds are administered topically.  
     
     
         42 . The method of  claim 38 , wherein the compounds are administered with a transdermal drug delivery agent.  
     
     
         43 . The method of  claim 42 , wherein the compounds are admixed with a lotion, cream, emulsion, oil, liquid, or gel, or embedded in a patch.  
     
     
         44 . The method of  claim 43 , wherein the compounds are admixed with a sunscreen cream.  
     
     
         45 . The method of  claim 38 , wherein the compounds are siRNAs, ribozymes, antisense nucleotides, transcription factor decoys, small molecules, or a combination thereof.  
     
     
         46 . The method of  claim 45 , wherein the third compound is an siRNA targeting  
       
         
           
                 
                 
                 
               
                     
                 
                   LIMK1 mRNA at 
                     
                     
                 
                   CCGCUACUGCCCCCCAAACUG, 
                   (SEQ ID NO:1) 
                 
                     
                 
                   CUGGCCGGCCACCUGCCACUG, 
                   (SEQ ID NO:2) 
                 
                     
                 
                   ACCGCUACUGCCCCCCAAACU, 
                   (SEQ ID NO:3) 
                 
                     
                 
                   CUGGCUCCCACCUGCCCCACA, 
                   (SEQ ID NO:4) 
                 
                     
                 
                   CCGAGACCUCAACUCCCACAA, 
                   (SEQ ID NO:5) 
                 
                     
                 
                   GGACCGCUACUGCCCCCCAAA, 
                   (SEQ ID NO:6) 
                 
                     
                 
                   CCGGCGCGGCGAGAGCGGACU, 
                   (SEQ ID NO:7) 
                 
                     
                 
                   GAGACCUCAACUCCCACAACU, 
                   (SEQ ID NO:8) 
                 
                     
                 
                   CUGCCCCCCGAGCUUCUUCCC, 
                   (SEQ ID NO:9) 
                 
                     
                 
                   UGGGUGCUCUGAGCAAAUCAC, 
                   (SEQ ID NO:10) 
                 
                   or 
                 
                     
                 
                   GGGCAGCUCUGCCCGGCAGAA, 
                   (SEQ ID NO:11) 
                 
                   or 
                 
                     
                 
                   an siRNA targeting dLIMK1 mRNA at 
                 
                   CAGCCGCCUGCUCCAGCUGAC, 
                   (SEQ ID NO:12) 
                 
                     
                 
                   CCAUGGGUGCUCUGAGCAAAU, 
                   (SEQ ID NO:13) 
                 
                     
                 
                   CAUGGGUGCUCUGAGCAAAUC, 
                   (SEQ ID NO:14) 
                 
                     
                 
                   AUGGGUGCUCUGAGCAAAUCA, 
                   (SEQ ID NO:15) 
                 
                     
                 
                   ACGGCCCACCGGGCUGUGGCA, 
                   (SEQ ID NO:16) 
                 
                     
                 
                   GUGGCACCGAGCACUCACACA, 
                   (SEQ ID NO:17) 
                 
                     
                 
                   AUGGCACGCCCAUCCGAAAUG, 
                   (SEQ ID NO:18) 
                 
                     
                 
                   UGGCACGCCCAUCCGAAAUGU, 
                   (SEQ ID NO:19) 
                 
                     
                 
                   CUGCCUCACGUGUGGGACCUU, 
                   (SEQ ID NO:20) 
                 
                     
                 
                   UCCCUGUCGCACCAGUACUAU, 
                   (SEQ ID NO:21) 
                 
                     
                 
                   CCCUGAGCUCUCCGGCUUAUA, 
                   (SEQ ID NO:22) 
                 
                   or 
                 
                     
                 
                   GCCUCACGUGUGGGACCUUUA, 
                   (SEQ ID NO:23) 
                 
                     
                 
                   and the sixth compound is an 
                 
                   siRNA targeting VEGF mRNA at 
                 
                   GCGCAGCUACUGCCAUCCAAU, 
                   (SEQ ID NO:24) 
                 
                     
                 
                   CAGCGCAGCUACUGCCAUCCA, 
                   (SEQ ID NO:25) 
                 
                     
                 
                   UUGGAGCCUUGCCUUGCUGCU, 
                   (SEQ ID NO:26) 
                 
                     
                 
                   CAGGCUGCACCCAUGGCAGAA, 
                   (SEQ ID NO:27) 
                 
                     
                 
                   GUGGGCCUUGCUCAGAGCGGA, 
                   (SEQ ID NO:28) 
                 
                     
                 
                   AGGCGAGGCAGCUUGAGUUAA, 
                   (SEQ ID NO:29) 
                 
                     
                 
                   GGCGAGGCAGCUUGAGUUAAA, 
                   (SEQ ID NO:30) 
                 
                     
                 
                   UUGCUCAGAGCGGAGAAAGCA, 
                   (SEQ ID NO:31) 
                 
                     
                 
                   UGCCCACUGAGGAGUCCAACA, 
                   (SEQ ID NO:32) 
                 
                   or 
                 
                     
                 
                   GCCCACUGAGGAGUCCAACAU. 
                   (SEQ ID NO:33) 
                 
                     
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         47 . A composition, comprising one or more therapeutic compounds and a transdermal drug delivery agent.  
     
     
         48 . The composition of  claim 47 , wherein the one or more compounds are admixed with a lotion, cream, emulsion, oil, liquid, or gel, or embedded in a patch.  
     
     
         49 . The composition of  claim 48 , wherein the one or more compounds are admixed with a sunscreen cream.  
     
     
         50 . The composition of  claim 47 , wherein the one or more compounds regulate the expression of one or more genes in a subject.  
     
     
         51 . The composition of  claim 50 , wherein the one or more genes are associated with cancer.  
     
     
         52 . The composition of  claim 51 , wherein the cancer is melanoma, breast cancer, colon cancer, lung cancer, or merkel cell carinoma.  
     
     
         53 . The composition of  claim 51 , wherein the one or more genes include CAV1, CST3, LIMK1, MMP2, MMP15, VEGF, ETV4, MMP9, PIK3C2B, SERPIN1, or a combination thereof.  
     
     
         54 . The composition of  claim 53 , wherein the one or more compounds include an siRNA targeting  
       
         
           
                 
                 
                 
               
                     
                 
                   LIMK1 mRNA at 
                     
                     
                 
                   CCGCUACUGCCCCCCAAACUG, 
                   (SEQ ID NO:1) 
                 
                     
                 
                   CUGGCCGGCCACCUGCCACUG, 
                   (SEQ ID NO:2) 
                 
                     
                 
                   ACCGCUACUGCCCCCCAAACU, 
                   (SEQ ID NO:3) 
                 
                     
                 
                   CUGGCUCCCACCUGCCCCACA, 
                   (SEQ ID NO:4) 
                 
                     
                 
                   CCGAGACCUCAACUCCCACAA, 
                   (SEQ ID NO:5) 
                 
                     
                 
                   GGACCGCUACUGCCCCCCAAA, 
                   (SEQ ID NO:6) 
                 
                     
                 
                   CCGGCGCGGCGAGAGCGGACU, 
                   (SEQ ID NO:7) 
                 
                     
                 
                   GAGACCUCAACUCCCACAACU, 
                   (SEQ ID NO:8) 
                 
                     
                 
                   CUGCCCCCCGAGCUUCUUCCC, 
                   (SEQ ID NO:9) 
                 
                     
                 
                   UGGGUGCUCUGAGCAAAUCAC, 
                   (SEQ ID NO:10) 
                 
                   or 
                 
                     
                 
                   GGGCAGCUCUGCCCGGCAGAA, 
                   (SEQ ID NO:11) 
                 
                     
                 
                   an siRNA targeting dLIMK1 mRNA at 
                 
                   CAGCCGCCUGCUCCAGCUGAC, 
                   (SEQ ID NO:12) 
                 
                     
                 
                   CCAUGGGUGCUCUGAGCAAAU, 
                   (SEQ ID NO:13) 
                 
                     
                 
                   CAUGGGUGCUCUGAGCAAAUC, 
                   (SEQ ID NO:14) 
                 
                     
                 
                   AUGGGUGCUCUGAGCAAAUCA, 
                   (SEQ ID NO:15) 
                 
                     
                 
                   ACGGCCCACCGGGCUGUGGCA, 
                   (SEO ID NO:16) 
                 
                     
                 
                   GUGGCACCGAGCACUCACACA, 
                   (SEQ ID NO:17) 
                 
                     
                 
                   AUGGCACGCCCAUCCGAAAUG, 
                   (SEQ ID NO:18) 
                 
                     
                 
                   UGGCACGCCCAUCCGAAAUGU, 
                   (SEQ ID NO:19) 
                 
                     
                 
                   CUGCCUCACGUGUGGGACCUU, 
                   (SEQ ID NO:20) 
                 
                     
                 
                   UCCCUGUCGCACCAGUACUAU, 
                   (SEQ ID NO:21) 
                 
                     
                 
                   CCCUGAGCUCUCCGGCUUAUA, 
                   (SEQ ID NO:22) 
                 
                   or 
                 
                     
                 
                   GCCUCACGUGUGGGACCUUUA, 
                   (SEQ ID NO:23) 
                 
                     
                 
                   an siRNA targeting VEGF mRNA at 
                 
                   GCGCAGCUACUGCCAUCCAAU, 
                   (SEQ ID NO:24) 
                 
                     
                 
                   CAGCGCAGCUACUGCCAUCCA, 
                   (SEQ ID NO:25) 
                 
                     
                 
                   UUGGAGCCUUGCCUUGCUGCU, 
                   (SEQ ID NO:26) 
                 
                     
                 
                   CAGGCUGCACCCAUGGCAGAA, 
                   (SEQ ID NO:27) 
                 
                     
                 
                   GUGGGCCUUGCUCAGAGCGGA, 
                   (SEQ ID NO:28) 
                 
                     
                 
                   AGGCGAGGCAGCUUGAGUUAA, 
                   (SEQ ID NO:29) 
                 
                     
                 
                   GGCGAGGCAGCUUGAGUUAAA, 
                   (SEQ ID NO:30) 
                 
                     
                 
                   UUGCUCAGAGCGGAGAAAGCA, 
                   (SEQ ID NO:31) 
                 
                     
                 
                   UGCCCACUGAGGAGUCCAACA, 
                   (SEQ ID NO:32) 
                 
                   or 
                 
                     
                 
                   GCCCACUGAGGAGUCCAACAU, 
                   (SEQ ID NO:33) 
                 
                   or 
                 
                     
                 
                   a combination thereof. 
                 
                     
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         55 . The composition of  claim 50 , wherein the one or more compounds are siRNAs, ribozymes, antisense nucleotides, transcription factor decoys, small molecules, or a combination thereof.  
     
     
         56 . A composition, comprising a combination of at least two compounds selected from the group consisting of a first compound that inhibits the expression of CAV1, a second compound that inhibits the expression of CST3, a third compound that inhibits the expression of LIMK1, a fourth compound that inhibits the expression of MMP2, a fifth compound that inhibits the expression of MMP15, a sixth compound that inhibits the expression of VEGF, a seventh compound that enhances the expression of ETV4, an eighth compound that enhances the expression of MMP9, a ninth compound that enhances the expression of PIK3C2B, and a tenth compound that enhances the expression of SERPIN1, wherein the combination is not a first combination of the third and fourth compounds, a second combination of the third and sixth compounds, a third combination of the fourth and sixth compounds, or a fourth combination of the third, fourth, and sixth compounds.  
     
     
         57 . The composition of  claim 56 , further comprising a transdermal drug delivery agent.  
     
     
         58 . The composition of  claim 57 , wherein the compounds are admixed with a lotion, cream, emulsion, oil, liquid, or gel, or embedded in a patch.  
     
     
         59 . The composition of  claim 58 , wherein the compounds are admixed with a sunscreen cream.  
     
     
         60 . The composition of  claim 56 , wherein the compounds are siRNAs, ribozymes, antisense nucleotides, transcription factor decoys, small molecules, or a combination thereof.  
     
     
         61 . The composition of  claim 60 , wherein the third compound is an siRNA targeting  
       
         
           
                 
                 
                 
               
                     
                 
                   LIMK1 mRNA at 
                     
                     
                 
                   CCGCUACUGCCCCCCAAACUG, 
                   (SEQ ID NO:1) 
                 
                     
                 
                   CUGGCCGGCCACCUGCCACUG, 
                   (SEQ ID NO:2) 
                 
                     
                 
                   ACCGCUACUGCCCCCCAAACU, 
                   (SEQ ID NO:3) 
                 
                     
                 
                   CUGGCUCCCACCUGCCCCACA, 
                   (SEQ ID NO:4) 
                 
                     
                 
                   CCGAGACCUCAACUCCCACAA, 
                   (SEQ ID NO:5) 
                 
                     
                 
                   GGACCGCUACUGCCCCCCAAA, 
                   (SEQ ID NO:6) 
                 
                     
                 
                   CCGGCGCGGCGAGAGCGGACU, 
                   (SEQ ID NO:7) 
                 
                     
                 
                   GAGACCUCAACUCCCACAACU, 
                   (SEQ ID NO:8) 
                 
                     
                 
                   CUGCCCCCCGAGCUUCUUCCC, 
                   (SEQ ID NO:9) 
                 
                     
                 
                   UGGGUGCUCUGAGCAAAUCAC, 
                   (SEQ ID NO:10) 
                 
                   or 
                 
                     
                 
                   GGGCAGCUCUGCCCGGCAGAA, 
                   (SEQ ID NO:11) 
                 
                   or 
                 
                     
                 
                   an siRNA targeting dLIMK1 mRNA at 
                 
                   CAGCCGCCUGCUCCAGCUGAC, 
                   (SEQ ID NO:12) 
                 
                     
                 
                   CCAUGGGUGCUCUGAGCAAAU, 
                   (SEQ ID NO:13) 
                 
                     
                 
                   CAUGGGUGCUCUGAGCAAAUC, 
                   (SEQ ID NO:14) 
                 
                     
                 
                   AUGGGUGCUCUGAGCAAAUCA, 
                   (SEQ ID NO:15) 
                 
                     
                 
                   ACGGCCCACCGGGCUGUGGCA, 
                   (SEQ ID NO:16) 
                 
                     
                 
                   GUGGCACCGAGCACUCACACA, 
                   (SEQ ID NO:17) 
                 
                     
                 
                   AUGGCACGCCCAUCCGAAAUG, 
                   (SEQ ID NO:18) 
                 
                     
                 
                   UGGCACGCCCAUCCGAAAUGU, 
                   (SEQ ID NO:19) 
                 
                     
                 
                   CUGCCUCACGUGUGGGACCUU, 
                   (SEQ ID NO:20) 
                 
                     
                 
                   UCCCUGUCGCACCAGUACUAU, 
                   (SEQ ID NO:21) 
                 
                     
                 
                   CCCUGAGCUCUCCGGCUUAUA, 
                   (SEQ ID NO:22) 
                 
                   or 
                 
                     
                 
                   GCCUCACGUGUGGGACCUUUA, 
                   (SEQ ID NO:23) 
                 
                     
                 
                   and the sixth compound is an 
                 
                   siRNA targeting VEGF mRNA at 
                 
                   GCGCAGCUACUGCCAUCCAAU, 
                   (SEQ ID NO:24) 
                 
                     
                 
                   CAGCGCAGCUACUGCCAUCCA, 
                   (SEQ ID NO:25) 
                 
                     
                 
                   UUGGAGCCUUGCCUUGCUGCU, 
                   (SEQ ID NO:26) 
                 
                     
                 
                   CAGGCUGCACCCAUGGCAGAA, 
                   (SEQ ID NO:27) 
                 
                     
                 
                   GUGGGCCUUGCUCAGAGCGGA, 
                   (SEQ ID NO:28) 
                 
                     
                 
                   AGGCGAGGCAGCUUGAGUUAA, 
                   (SEQ ID NO:29) 
                 
                     
                 
                   GGCGAGGCAGCUUGAGUUAAA, 
                   (SEQ ID NO:30) 
                 
                     
                 
                   UUGCUCAGAGCGGAGAAAGCA, 
                   (SEQ ID NO:31) 
                 
                     
                 
                   UGCCCACUGAGGAGUCCAACA, 
                   (SEQ ID NO:32) 
                 
                   or 
                 
                     
                 
                   GCCCACUGAGGAGUCCAACAU. 
                   (SEQ ID NO:33) 
                 
                     
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         62 . A kit, consisting of a combination of at least two agents selected from the group consisting of a first agent for detecting the expression of CAV1, a second agent for detecting the expression of CST3, a third agent for detecting the expression of LIMK1, a fourth agent for detecting the expression of MMP2, a fifth agent for detecting the expression of MMP15, a sixth agent for detecting the expression of VEGF, a seventh agent for detecting the expression of ETV4, an eighth agent for detecting the expression of MMP9, a ninth agent for detecting the expression of PIK3C2B, and a tenth agent for detecting the expression of SERPIN1, wherein the combination is not a first combination of the third and fourth agents, a second combination of the third and sixth agents, a third combination of the fourth and sixth agents, or a fourth combination of the third, fourth, and sixth agents.

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