A tHeranostic approach to reduce local recurrence of MYxofibrosaRcomA (HYdRA)

Photodynamic therapy (PDT) is an approved cancer treatment worldwide that uses targeted, harmless red light to activate non-toxic photosensitizers. This innovative and minimally invasive method induces cytotoxic effects in diseased areas by promoting the production of reactive oxygen species while preserving healthy tissues. Despite advancements in surgical practices, achieving complete microscopic resection remains challenging, often leading to local relapse. Therefore, combining fluorescence-guided microsurgery (FGMS) with PDT could be a promising strategy to eradicate resectable tumors with a high risk of recurrence.

This project aims to provide preclinical proof of the applicability of FGMS coupled with PDT in treating Myxofibrosarcoma (MFS) and Osteosarcoma (OS), the main representative subtypes of soft tissues and bone sarcomas, prone to relapse after surgery. We tested a panel of photosensitizers (PSs) that can be photoactivated with light in the 630-660 nm wavelengths’ range in in vitro 2D and 3D models of MFS and OS cell lines, along with ex-vivo patient-derived samples and in vivo xenograft zebrafish embryos. The PSs were ranked on (a) selective uptake by tumor cells, compared to healthy cells and (b) the cytotoxic effect, after irradiation. 

Hence, these results provide a preclinical proof of concept for a novel therapeutic approach that effectively could eradicate MFS and OS inducing cytotoxic effects in cancer cells while preserving healthy tissue. This approach could reduce cancer recurrence and pave the way for extending this strategy to other pathologies.