Inhibition of usp14 impairs melanoma cell survival and overcomes resistance to mapk-targeting therapies

The present invention relates to a method and composition for treating melanoma. More particularly, inventors have shown that high expression of USP14 correlates with melanoma progression and with a poorer survival rate in metastatic melanoma patients. Then, they have shown that when ubiquitin-specific peptidase 14 (USP14) is inhibited by siRNAs and pharmacological inhibitors (b-AP15, WP1130 and HBX41108), the cell proliferation of melanoma cell drastically decreased. They have also shown that melanoma treatment with pharmacological inhibitors can overcome resistance to drugs targeting oncogenic BRAF. Accordingly, the invention relates to a method for predicting the survival time of a subject suffering from melanoma by quantifying the expression level of USP14 in a biological sample and to a method of treating melanoma and resistant melanoma by using the inhibitors of USP14. Targeting the proteasome-associated deubiquitinating enzyme USP14 induces melanoma cell death and overcomes resistance to MAPK-targeting therapies in vitro/in vivo.

Keywords: ubiquitin-proteasome, deubiquitinase, USP14, MAPK-targeting therapies
Patent Application number: EP17305339.8
Inventors:
Robin DIDIERMarcel DECKERTAude MALLAVIALLESophie TARTARE-DECKERT
Publications:
Mol Cancer Ther. 2018 Apr 27. pii: molcanther.0919.2017. doi: 10.1158/1535-7163.MCT-17-0919. [Epub ahead of print]

Reference:

BIO16432-T1

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Patent filling date: 2017-03-24

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