Fusion proteins and methods thereof
The invention discloses oncogenic fusion proteins. The invention provides methods for treating gene-fusion based cancers.
1. A method for treating a FGFR3-TACC3 fusion associated cancer in a subject in need thereof, the method comprising administering to the subject an effective amount of JNJ-42756493, wherein the subject has a FGFR3-TACC3 fusion associated cancer, wherein the FGFR3-TACC3 fusion comprises a tyrosine kinase domain of FGFR3 fused to the TACC domain of transforming acidic coiled-coil-containing (TACC)3.
2. The method of claim 1 , wherein the subject has FGFR3-TACC3 fusion associated epithelial cancer, glioma, glioblastoma multiforme, breast cancer, lung cancer, prostate cancer, bladder carcinoma, squamous lung carcinoma, head and neck carcinoma or colorectal carcinoma.
3. The method of claim 1 , wherein the subject has FGFR3-TACC3 fusion associated epithelial cancer.
4. The method of claim 1 , wherein the subject has FGFR3-TACC3 fusion associated glioblastoma multiforme.
5. The method of claim 1 , wherein the subject has FGFR3-TACC3 fusion associated glioma.
6. The method of claim 5 , wherein the glioma is a grade II or III glioma.
7. The method of claim 4 , wherein the subject does not have mutations in IDH1 or IDH2 genes.
8. The method of claim 4 , wherein the subject does not have a gene amplification in EGFR.
9. The method of claim 4 , wherein the subject does not express EGFRγIII transcript variant.
10. The method of claim 4 , wherein the subject has a gene amplification of CDK4, MDM2, or both.
11. The method of claim 1 , wherein the FGFR3-TACC3 fusion comprises SEQ ID NO: 85, 86, 87, or 89.
12. The method of claim 1 , wherein the FGFR3-TACC3 fusion comprises SEQ ID NO: 85.
13. The method of claim 1 , wherein the FGFR3-TACC3 fusion comprises SEQ ID NO: 87.
14. The method of claim 1 , wherein the FGFR3-TACC3 fusion comprises SEQ ID NO: 158, 159, 160, or 161.
15. The method of claim 1 , wherein the FGFR3-TACC3 fusion comprises SEQ ID NO: 542, 543, 544, 545, 546, or 547.
16. The method of claim 1 , wherein the FGFR3-TACC3 fusion comprises a tyrosine kinase domain of FGFR3 transcript variant 1 fused to the TACC domain of TACC3.
17. The method of claim 1 , wherein a nucleotide sequence encoding the FGFR3-TACC3 fusion comprises SEQ ID NO: 1-77, 80-82, or 84.
18. The method of claim 1 , wherein a nucleotide sequence encoding the FGFR3-TACC3 fusion comprises SEQ ID NO: 519-527, or 530-538.
19. The method of claim 1 , wherein a nucleotide sequence encoding the FGFR3-TACC3 fusion comprises SEQ ID NO: 533-538.
20. A method for diagnosing and treating a FGFR3-TACC3 fusion associated cancer in a subject in need thereof, the method comprising:
a. obtaining a biological sample from the subject;
b. detecting whether the subject has a FGFR3-TACC3 fusion is present in the biological sample, wherein the FGFR3-TACC3 fusion comprises a tyrosine kinase domain of FGFR3 fused to the TACC domain of transforming acidic coiled-coil-containing (TACC) 3; and
c. diagnosing the subject with a FGFR3-TACC3 fusion associated cancer when the presence of the FGFR3-TACC3 fusion in the biological sample is detected; then
d. administering to the subject an effective amount of JNJ-42756493.
21. The method of claim 6 , wherein the subject does not have mutations in IDH1 or IDH2 genes.
22. The method of claim 6 , wherein the subject does not have a gene amplification in EGFR.
23. The method of claim 6 , wherein the subject does not express EGFRγIII transcript variant.
24. The method of claim 6 , wherein the subject has a gene amplification of CDK4, MDM2, or both.