Ruthenium-Based photoactivated chemotherapy against eye cancer
The Ru4EYE PoC proposal will develop the first pre-clinical evaluation of Ru-based PACT compounds in uveal melanoma (UM) model. UM is a rare malignancy of the eye. Although treatment against UM do exist, they do no always preserve vision or the eye, and often lead to patient death via metastasis to the liver. A better treatment that would save vision, the eye, and the patient, is looked after. UM appears as an appealing disease for photoactivated chemotherapy (PACT), a new form of phototherapy developed within my ERC Starting Grant RuProLight. PACT agents are photosensitive compounds that can kill cancer cells selectively under the action of light. In PACT dioxygen does not need to be present at the site of light irradiation because the mechanism of photochemical activation is an oxygen-independent bond breakage reaction between a bioactive, cytotoxic agent, and a light-removable protecting group. Innovative therapeutic solutions such as PACT are typically difficult to bring to the market because of the risky nature of drug development and the funding required for clinical trials. The vision in this grant proposal is that positive results on a rare form of cancer such as uveal melanoma could not only offer a relatively short-term solution to uveal melanoma patients, but also accelerate translation of Ru-based PACT to the clinics by driving developments for other diseases as well. The biological testing of Ru-based PACT compounds will be performed in a complete series of translational cancer models: from in vitro (2D monolayers of normoxic and hypoxic cancer cells, 3D tumor spheroids) to in vivo (xenografts in zebrafish embryo for studying metastasis formation and treatment, and mouse model for in vivo toxicity and efficacy). The aim is to develop a pre-clinical proof-of-concept that PACT can be used to treat uveal melanoma, so that presentation to venture capital and clinical testing can start quickly after completion of the project.