Periodic Reporting for period 1 - MELASTOP (Discovery of mevalonate and UBIAD1 inhibitors as novel drugs targeting melanoma skin cancer)
Reporting period: 2021-07-01 to 2024-06-30
Since melanoma is the most aggressive skin tumor, there is an urgent need for development of novel drugs that can cure and prolong the survival of melanoma patients. In this ERC-PoC grant named MELASTOP we have investigatesd the mevalonate metabolic pathway as a new target to inactivate in melanoma patients. In details we have discovered that the mevalonate enzyme, UBIAD1, has antioxidant properties and are critical caretaker of oxidative stress and ferroptosis in human melanoma cells and possibly during melanoma progression. Therefore in this project we have tested and validated specific mevalonate inhibitors, such as statins and parabens derivatives (UBIAD1i) as novel therapeutic drugs to treat melanoma resistance. Using both in vitro and in vio studies we did not score significant tumor regression in all animals treated with statin therapies. On the other side, UBIAD1i treatment induces severe stress at different doses suggesting some sort of toxicity effect that will not allow to draft any conclusions. Overall, although encouraging more work is needed to design and test new mevalonate and UBIAD1 inhibitors working in in vivo settings to successfully develop the work related to IP and commercialization.