HypoRuLight · Hypoxic Tumour Models for Photoactivatable Ruthenium-based Chemotherapy

In this Proof-of-Concept project I will show the commercial potential of ruthenium-based photoactivated chemotherapy (PACT) compounds developed in my ERC Starting Grant by demonstrating their efficacy on hypoxic cancer models. Photoactivated chemotherapy is a new class of phototherapy to treat cancer. In principle, PACT looks similar to photodynamic therapy (PDT): light irradiation of the tumour in vivo leads to local activation of the anticancer prodrug, thereby limiting the toxicity of the treatment to the diseased tissue, and thus lowering side effects for the patient. However, the mechanisms of PACT and PDT are very different: in PDT the light-absorbing prodrug requires molecular oxygen to kill the cancer cells, whereas in PACT oxygen is not involved in prodrug activation. As a consequence, PACT agents should be able to treat hypoxic tumours, which are characterized by low oxygen concentrations and high resistance to PDT and other existing therapies. In this project the efficacy of a selection of Ru-based PACT compounds will be tested in hypoxic cancer models and compared to their efficacy in normoxic conditions. In parallel I will develop, in collaboration with my network of collaborators from the clinics, business analysts, and patent attorney, a plan for (pre) clinical development of PACT compounds.