Targeted therapy to block melanoma progression through peptide phage-display profiling of melanoma cells and derived extracellular vesicles

Descripción del proyecto

Una estrategia de doble objetivo contra el melanoma metastásico

El melanoma se caracteriza por una mayor propensión a la metástasis y a desarrollar resistencia a los tratamientos existentes. Cada vez hay más pruebas de que el receptor del factor de crecimiento nervioso p75NTR impulsa la progresión, invasión y metástasis del melanoma, lo que lo convierte en una diana terapéutica atractiva. El equipo del proyecto Target-MelaneX, financiado con fondos europeos, propone desarrollar una estrategia de inhibición dual de p75NTR dirigida a células de melanoma y vesículas extracelulares. Se sabe que las vesículas extracelulares desempeñan un papel clave en la comunicación entre células, pero también impulsan la metástasis. Los investigadores planean desarrollar ligandos peptídicos que se unan selectivamente y bloqueen la función de p75NTR, lo que abrirá nuevas vías para el tratamiento del melanoma metastásico.

Objetivo

Melanoma, the deadliest form of skin cancer, is strongly influenced by environmental factors such as UV radiation from ozone depletion. In 2022, there were 331,722 new melanoma cases globally, and by 2040, cases are expected to rise by 50%. A major challenge in treating melanoma is its ability to metastasize, especially when therapeutic targets are unclear or when tumors develop resistance to existing treatments. Recent research findings have identified the nerve growth factor receptor p75NTR as a key player in melanoma progression, invasion, and metastasis, especially in highly metastatic melanoma cells. This project aims to target p75NTR in melanoma cells and extracellular vesicles (EVs) to inhibit melanoma progression.

While p75NTR role has been identified in melanoma cells, its role in tumor-derived EVs—responsible for cell communication and metastasis—remains under-explored. This project aims to block p75NTR in both melanoma cells and EVs, where co-receptors and co-effectors availability and cellular interactions differ from that within cells, potentially offering a new therapeutic approach. Leveraging phage display technique, the project will identify peptide ligands specific to p75NTR on melanoma cells and EVs.

Outcomes from this Fellowship will benefit several scientific communities, including those working in biomaterials and peptide sciences and, cancer, while providing advanced training and career development opportunities for a young researcher at the intersection of targeted cancer therapies, advanced biomaterials design and peptide technology, preparing her for a leadership role in translational cancer research. By addressing both melanoma cells and EVs, this project introduces a dual-targeted strategy with the potential to transform the understanding of melanoma biology and open new avenues for more effective therapies.