Periodic Reporting for period 1 - HypoRuLight (Hypoxic Tumour Models for Photoactivatable Ruthenium-based Chemotherapy)
Période du rapport: 2017-10-01 au 2019-03-31
In this project, studies have been realised to move forward ruthenium-based photo activated chemotherapy (PACT) compounds towards the clinics.
In a first part of the project, synthetic work has been performed to prepare 4 different ruthenium-based PACT compounds on a scale close to one gram without column chromatography. Column chromatography is a purification technique often used in fundamental research labs to purify new compounds. It is very efficient and allows getting small amounts of highly pure compounds, but it is very difficult to produce real drugs on a drug-like scale (say, 1, 10, or 100 kg) using chromatography techniques. Our results show that Ru-based PACT compounds can indeed be synthesised without chromatography, which brings them one step closer to real application.
Second, a market study has been realised in collaboration with a private consulting company specialised in oncology, to determine which forms of cancer are best suited for real life application of PACT compounds. From this market study it turns out that head-and-neck cancer, liver cancer, non-melanoma skin cancer, brain cancer, and certain forms of eye cancer, are the diseases that offer the best chances for PACT compounds to reach the market. We now exclusively focus on these cancer types to test the biological properties of all our PACT compounds.
Finally, a protocol has been developed to study the efficacy of PACT compounds in 3D tumor spheroids. Most drug efficacy tests are realised in two dimensional cell monolayers, which does not represent very well the conditions met by cancer cells in a real tumor. 3D tumor spheroids, on the contrary, offer more heterogeneity, not only in terms of cell population, but also in terms of dioxygen concentration within the spheroid and in terms of nutrient concentration. Our team can now use this newly established protocol to study the efficacy of our compounds in a more realistic model of cancer.
In a first part of the project, synthetic work has been performed to prepare 4 different ruthenium-based PACT compounds on a scale close to one gram without column chromatography. Column chromatography is a purification technique often used in fundamental research labs to purify new compounds. It is very efficient and allows getting small amounts of highly pure compounds, but it is very difficult to produce real drugs on a drug-like scale (say, 1, 10, or 100 kg) using chromatography techniques. Our results show that Ru-based PACT compounds can indeed be synthesised without chromatography, which brings them one step closer to real application.
Second, a market study has been realised in collaboration with a private consulting company specialised in oncology, to determine which forms of cancer are best suited for real life application of PACT compounds. From this market study it turns out that head-and-neck cancer, liver cancer, non-melanoma skin cancer, brain cancer, and certain forms of eye cancer, are the diseases that offer the best chances for PACT compounds to reach the market. We now exclusively focus on these cancer types to test the biological properties of all our PACT compounds.
Finally, a protocol has been developed to study the efficacy of PACT compounds in 3D tumor spheroids. Most drug efficacy tests are realised in two dimensional cell monolayers, which does not represent very well the conditions met by cancer cells in a real tumor. 3D tumor spheroids, on the contrary, offer more heterogeneity, not only in terms of cell population, but also in terms of dioxygen concentration within the spheroid and in terms of nutrient concentration. Our team can now use this newly established protocol to study the efficacy of our compounds in a more realistic model of cancer.