UTILITY OF RET MUTANT IN DIAGNOSIS AND TREATMENT OF MELANOMA
The invention relates to a method of detecting a RET mutant in a melanoma cell. Also disclosed is a method of modulating the activity of a RET mutant in a melanoma cell with an agent that interferes with the activity of the RET mutant.
1 . A method of modulating the activity of a RET mutant in a melanoma cell, comprising:
providing a melanoma cell containing a RET mutant; and
contacting the cell with an agent that interferes with the activity of the RET mutant.
2 . The method of claim 1 , wherein the RET mutant is RETmt (RET G691S).
3 . The method of claim 1 , wherein the melanoma cell further contains a BRAF mutant.
4 . The method of claim 3 , wherein the BRAF mutant is BRAFmt.
5 . The method of claim 1 , wherein the agent interferes with the interaction between the RET mutant and GDNF (glial cell line-derived neurotrophic factor).
6 . The method of claim 1 , wherein the agent interferes with the signal transduction through a pathway comprising the RET mutant and RAS (rat sarcoma).
7 . The method of claim 6 , wherein the agent interferes with cell proliferation, migration, or invasion, or the phosphorylation of ERK1/2 (Extracellular Signal-Regulated Kinase 1/2).
8 . The method of claim 1 , wherein the agent interferes with the signal transduction through a pathway comprising the RET mutant and PI3K (phosphatidylinositol-3-Kinase).
9 . The method of claim 8 , wherein the agent interferes with cell proliferation, migration, or invasion, or the phosphorylation of Akt (protein kinase B).
10 . The method of claim 1 , wherein the agent is a RTK (receptor tyrosine kinase) inhibitor.
11 . The method of claim 10 , wherein the RTK inhibitor is sorafenib or semaxanib.
12 . The method of claim 1 , wherein the agent is an antibody, peptide, or siRNA against the RET mutant.