NUMB splicing modulation with AONs as a novel lung cancer treatment

Lung cancer is the leading cause of cancer death worldwide and an unmet medical need. Although novel targeted therapies have been developed against its main driver mutations, they have not proven sufficiently effective in the clinics. Research from Valcárcel’s group suggests a novel mechanism based on the modulation of NUMB alternative splicing to target lung cancer. The aim of the project is to characterize the efficacy of NUMB exon 9 alternative splicing modulation as a putative therapeutic approach in several sub-types of lung cancer, with a focus on non-KRas-driven lung adenocarcinomas and on lung squamous cell cancers. Saturation mutagenesis, bioinformatic analyses and biochemical and molecular approaches will serve to better understand how this splicing event is regulated through key sequence regulatory elements and factors. This, together with testing the efficacy of NUMB splicing modulation in different genetic backgrounds in vitro and in vivo will allow us to stratify those patients that could hopefully benefit from a NUMB splicing modulation therapy.