Fusion proteins and methods thereof

Abstract

The invention discloses oncogenic fusion proteins. The invention provides methods for treating gene-fusion based cancers.

What is claimed is: 
     
         1 . A cDNA encoding a fusion protein comprising the tyrosine kinase domain of EGFR fused to:
 (i) a phosphoserine phosphatase (PSPH) protein; or   (ii) a Cullin-associated and neddylation-dissociated (CAND) protein.   
     
     
         2 . The cDNA of  claim 1 , wherein the CAND protein is CAND protein is CAND1, CAND2, or CAND3. 
     
     
         3 . The cDNA of  claim 1 , wherein the CAND protein is CAND1. 
     
     
         4 . The cDNA of  claim 1 , wherein the fusion protein is EGFR-CAND1 or EGFR-PSPH. 
     
     
         5 . The cDNA of  claim 1 , wherein the cDNA comprising the tyrosine kinase domain of EGFR fused to a PSPH protein comprises SEQ ID NO: 8 or SEQ ID NO: 10 or has a genomic breakpoint comprising SEQ ID NO: 10. 
     
     
         6 . The cDNA of  claim 1 , wherein the cDNA comprising the tyrosine kinase domain of EGFR fused to a CAND protein comprises SEQ ID NO: 14 or SEQ ID NO: 15, or has a genomic breakpoint comprising SEQ ID NO: 15. 
     
     
         7 . A purified fusion protein comprising the tyrosine kinase domain of EGFR fused to:
 (i) a phosphoserine phosphatase (PSPH) protein; or   (ii) a Cullin-associated and neddylation-dissociated (CAND) protein.   
     
     
         8 . The purified fusion protein of  claim 7 , wherein the fusion protein is EGFR-CAND1 or EGFR-PSPH. 
     
     
         9 . The purified fusion protein of  claim 7 , wherein the fusion protein comprises SEQ ID NO: 7, 11, 13, or 8495. 
     
     
         10 . A method of decreasing growth of a solid tumor in a subject in need thereof, the method comprising administering to the subject an effective amount of an EGFR fusion molecule inhibitor, wherein the inhibitor decreases the size of the solid tumor, and wherein the EGFR fusion comprises the tyrosine kinase domain of EGFR fused to:
 (i) the coiled-coil domain of a Septin protein;   (ii) a phosphoserine phosphatase (PSPH) protein; or   (iii) a Cullin-associated and neddylation-dissociated (CAND) protein.   
     
     
         11 . The method of  claim 10 , wherein the solid tumor comprises glioblastoma multiforme, breast cancer, lung cancer, prostate cancer, or colorectal carcinoma. 
     
     
         12 . The method of  claim 11 , wherein the solid tumor comprises glioblastoma multiforme. 
     
     
         13 . The method of  claim 10 , wherein the inhibitor comprises an antibody that specifically binds to an EGFR-SEPT fusion protein, an EGFR-PSPH fusion protein, an EGFR-CAND fusion protein, or a fragment thereof. 
     
     
         14 . The method of  claim 10 , wherein the inhibitor comprises a small molecule that specifically binds to an EGFR protein. 
     
     
         15 . The method of  claim 10 , wherein the inhibitor comprises an antisense RNA or antisense DNA that decreases expression of an EGFR-SEPT fusion protein, an EGFR-PSPH fusion protein, or an EGFR-CAND fusion protein. 
     
     
         16 . The method of  claim 10 , wherein the inhibitor comprises a siRNA that specifically targets an EGFR-SEPT fusion gene, an EGFR-PSPH fusion gene, or an EGFR-CAND fusion gene; or a combination thereof. 
     
     
         17 . The method of  claim 10 , wherein the fusion protein is EGFR-SEPT14, EGFR-CAND1, or EGFR-PSPH. 
     
     
         18 . The method of  claim 14 , wherein the small molecule that specifically binds to an EGFR protein comprises AZD4547, NVP-BGJ398, PD173074, NF449, TK1258, BIBF-1120, BMS-582664, AZD-2171, TSU68, AB1010, AP24534, E-7080, LY2874455, or a combination thereof.