Thesis presented October 15, 2024

Abstract:
Lung cancer is the leading cause of cancer-related deaths worldwide, with a mortality rate of 1.8 million people in 2020, according to data from the World Health Organization. Current research highlights the critical role of copper (Cu) in the proliferation and survival of cancer cells, emphasizing the importance of targeting its metabolism as a new therapeutic approach. In this context, our laboratory has co-developed an innovative class of molecules, Cu(I) ionophores, among which "Cuphoralix" stands out due to its ability to specifically interfere with copper metabolism in lung cancer cells. Our in vitro studies reveal that Cuphoralix induces irreversible cell cycle arrest and disrupts key signaling pathways involved in cell migration and proliferation. The synergistic combination of Cuphoralix with Cu+ salts has proven particularly effective in inhibiting lung cancer cell proliferation by altering the intracellular distribution of copper and inducing significant metal stress. Furthermore, the lipophilic nature of Cuphoralix directed our research towards the development of fusogenic and endocytic liposomes to optimize the delivery of this molecule. This strategy has led to the creation of formulations suitable for in vivo preclinical studies aimed at evaluating the toxicity and anti-tumor efficacy of Cuphoralix. The results obtained from subcutaneous xenograft models in mice illustrate the potential of our approach for lung cancer treatment, paving the way for promising therapeutic developments.

Keywords:
Lung cancer, Drug discovery, Trace elements, Cell signalling, Liposomes
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