Preclinical validation of a single-treatment infusion modality that can eradicate extremity melanomas

Menée sur un modèle murin de mélanome des extrémités, cette étude évalue, par rapport au melphalan, l'efficacité et la toxicité d'un nouvel anticancéreux (CBL0137) administrable par perfusion isolée du membre atteint

Résumé en anglais

Isolated limb perfusion (ILP) with the chemotherapeutic agent melphalan is an effective treatment option for extremity in-transit melanoma, but is toxic and technically challenging to deliver locoregionally. CBL0137 is an experimental clinical drug with broad anticancer activity in animal models, owing to its ability to bind DNA in a non-genotoxic manner and inactivate the FACT chromatin modulator essential for tumor cell viability. Here we report that CBL0137 delivered by ILP in a murine melanoma model is as efficacious as melphalan, displaying antitumor activity at doses corresponding to only a fraction of the systemic MTD of CBL0137. The ability to bind DNA quickly combined with a favorable safety profile made it possible to substitute CBL0137 in the ILP protocol, using an intra-arterial infusion method, to safely achieve effective tumor suppression. Our findings of a preclinical proof of concept for CBL0137 and its administration via intra-arterial infusion as a superior treatment compared to melphalan ILP, allows for locoregional treatment anywhere a catheter can be placed.