Methods and pharmaceutical compositions for the treatment of cancers associated with activation of the MAPK pathway

US11471538B2 · kind B2 · utility

Assignees

• INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) · FR
• UNIVERSITE PAUL SABATIER—TOULOUSE III · FR
• CENTRE HOSPITALIER UNIVERSITAIRE DE TOULOUSE · FR

Inventors

• Gilles FAVRE · Toulouse, FR
• Magdalena POHORECKA · Toulouse, FR

Key dates

• Filing date: Feb 9, 2018
• Grant date: Oct 18, 2022
• Expiry date: Mar 26, 2038

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C12Q2600/158
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

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 10 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 15 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.