Slitrk6 as a target for cancers associated with activation of the mapk pathway

The response of subjects suffering from cancer to MAPK inhibitors is dramatically impaired by secondary resistances and rapid relapse. So far, the molecular mechanisms driving these resistances are not completely understood. The inventors show that expression of SLITRK6 (SLIT and NTRK-like family, member 6) is induced by a MAPK inhibitor (e.g. Vemurafenib) and the inhibition of its induction in presence of the MAPK inhibitor induces synthetic lethality. Thus, the only inhibition of SLITRK6 by an inhibitor of activity or expression should potentiate the antitumor effect of the MAPK inhibitors and avoid the emergence of a resistance to those compounds. Furthermore the specific expression of SLITRK6 also paves the way of strategies based on depletion of the residual cancer cells by targeting them with anti-SLITRK6 antibodies capable of mediating ADCC or antibody-drug conjugates binding to SLITRK6.

Patent Application number: EP17305153.3

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