Descripción del proyecto
Tecnología de oligonucleótidos antisentido en el tratamiento del adenocarcinoma pulmonar
El adenocarcinoma pulmonar (LUAD, por sus siglas en inglés) es una forma agresiva de cáncer de pulmón con un mal pronóstico que representa un tercio de todos los casos de cáncer de pulmón y actualmente carece de terapias dirigidas para su tratamiento. Como resultado de un empalme alternativo, la gran mayoría de los LUAD tienen una isoforma de proteína Numb que impulsa la proliferación de células cancerosas y se correlaciona con un peor pronóstico de la enfermedad. Los oligonucleótidos antisentido (OAS) patentados que se desarrollaron previamente pudieron corregir el empalme patológico e inhibir la proliferación de células cancerosas y el crecimiento tumoral en varios modelos murinos. El proyecto TAONas-LUAD, financiado con fondos europeos, preparará la tecnología de OAS para los ensayos de validación clínica y desarrollará un plan de negocio para la comercialización.
Objetivo
Lung cancer is the leading cause of cancer-related deaths, with 1.8 million deaths expected globally in 2021. Lung adenocarcinomas (LUAD) represent 1/3 of all lung cancer cases. Despite notable advances, current treatments remain ineffective, resulting in <25% survival beyond 5 years. Due to the high heterogeneity of molecular abnormalities driving lung cancers, targeted therapies are applicable to only a small subset of patients. There is therefore an urgent unmet need for developing novel therapeutic approaches generally applicable to LUAD patients.
Alternative pre-mRNA splicing (AS) allows the synthesis of different protein variants from a single gene by differential selection of exonic sequences. Increased inclusion of exon 9 of the gene NUMB encodes a protein isoform that promotes cancer cell proliferation. This occurs in the vast majority of LUAD tumours, correlating with worse disease prognosis. Supported by the ERC PoC VALSL, we developed an innovative therapeutic approach based on the use of Antisense Oligonucleotides (AONs) that regulate NUMB AS. Our proprietary AONs correct NUMB pathological splicing, inhibit cancer cell proliferation and reduce tumour growth in four different mouse models of LUAD, including 2 Patient-Derived Xenograft models.
With support from the EIC Transition, we will bring this technology to a stage where it is ready to be validated in clinical trials. We will optimise our lead AONs by improving their chemistry, formulation and administration and will carry out regulatory pre-clinical studies. These will pave the way to the first application of AON-based splicing modulation in clinical oncology. To commercialise this technology, we also aim to develop the business plan for a spin-off company, AON Therapeutics. In the long term, our project has the potential to generate compounds, presentations and delivery methods that can be applicable to other target AS events and/or cancer types, as well as to other AS-related diseases.
Ámbito científico
Palabras clave
Programa(s)
- HORIZON.3.1 - The European Innovation Council (EIC) Main Programme
Convocatoria de propuestas
HORIZON-EIC-2021-TRANSITIONOPEN-01
Consulte otros proyectos de esta convocatoriaRégimen de financiación
HORIZON-EIC - HORIZON EIC GrantsCoordinador
08003 Barcelona
España