Alternative splicing is a major mechanism of gene regulation in cells that contain a nucleus. Alternative splicing allows a single gene to produce different proteins with similar, different or even opposite functions. Alterations in alternative splicing have been associated to a plethora of diseases, from retinal or nervous system degeneration to and cancer.
In particular, in lung cancer several splicing alterations contribute to tumor progression, including one on the gene NUMB. NUMB, through its alternative splicing variants, controls cancer cell proliferation. In our laboratory we have designed a battery of alternative splicing-modifying antisense oligonucleotides (AONs) capable of correcting this alteration.
The aim of our VALSL proposal was to assess the potential therapeutic use of these AONs for the treatment of lung cancer. Lung cancer is the leading cause of cancer death worldwide, with huge direct and indirect costs. Due to its high incidence and lack of effective therapies and it is considered an unmet medical need.
The VALSL project has allowed to perform key experiments to prove the potential application of these AONs in mouse models of the disease, including proof of concept studies about their efficacy, toxicity and administration route. It has allowed us to design a strategy to further develop the project through the creation of a spin-off company.
