Objetivo Lung squamous cell carcinoma (LSCC) represents one third of lung tumours; 550,000 cases are diagnosed annually worldwide (20% occur in Europe). Treatment options for this cancer type are still scarce. Identification of LSCC genetic drivers is thus an essential unmet need for developing novel therapies for this disease.In a stepwise multidisciplinary approach, we will determine if TNIK (Traf-2 and Nck-interacting kinase), a gene amplified in almost 40% of LSCC cases, constitutes a therapeutic target for the treatment of LSCC patients. Our preliminary data show that TNIK is overexpressed in LSCC cells, in which it has a pro-oncogenic role. Using proteomics approaches and functional assays, we will define the molecular mechanisms and critical signalling pathways that TNIK modulates to promote LSCC progression. In xenograft models we will confirm the contribution of TNIK to the studied phenotypes in vivo. We will analyse TNIK levels and activity (after identification of substrates) in patient samples, and will aim to validate TNIK as a target for therapeutic intervention using small molecule TNIK inhibitors in novel preclinical models: LSCC organoids and patient-derived xenografts. Finally, we will assess if increased TNIK expression can serve as a biomarker to select patients that would benefit from treatment with TNIK inhibitors. Our studies will increase our knowledge on LSCC biology and aim to find a precise treatment for this disease.This project will enable Dr P Torres-Ayuso to develop a wide range of new and transferable skills, and will allow him to broaden his technical, mentoring, management and communication skills. He will benefit from the high calibre of the Cancer Research UK Manchester Institute, and the expertise of his supervisor (Dr J Brognard) who will aid in his development as a young scientist. This project will thus enable the Fellow to achieve his long-term objective of obtaining a leadership position in a competitive European Institute. Ámbito científico medical and health sciencesclinical medicineoncologyskin cancer Palabras clave Lung squamous cell carcinoma targeted therapies driver genes protein kinases cell signalling Programa(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Tema(s) MSCA-IF-2015-EF - Marie Skłodowska-Curie Individual Fellowships (IF-EF) Convocatoria de propuestas H2020-MSCA-IF-2015 Consulte otros proyectos de esta convocatoria Régimen de financiación MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF) Coordinador THE UNIVERSITY OF MANCHESTER Aportación neta de la UEn € 183 454,80 Dirección OXFORD ROAD M13 9PL Manchester Reino Unido Ver en el mapa Región North West (England) Greater Manchester Manchester Tipo de actividad Higher or Secondary Education Establishments Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Participación en los programas de I+D de la UE Opens in new window Red de colaboración de HORIZON Opens in new window Coste total € 183 454,80
