Mitochondrial one-carbon metabolism as a therapeutic target in reducing cancer metastasis

Descrizione del progetto

Metastasi tumorali: bersagliare il metabolismo monocarbonioso mitocondriale

Comprendere le dipendenze metaboliche nelle metastasi, la principale causa di morte per i pazienti oncologici, è una sfida per la terapia oncologica. Ricerche recenti hanno dimostrato che il metabolismo mitocondriale a un carbonio (1C), che porta a un eccesso di formiato, aumenta l’invasività delle cellule tumorali. Tuttavia, non sono ancora state definite strategie efficaci per colpire questa via. Con il sostegno del programma di azioni Marie Skłodowska-Curie, il progetto Target-C1 adotterà un approccio multidisciplinare per affrontare il metabolismo 1C e i suoi effetti pro-invasivi causati dall’eccesso di formiato nel cancro. L’obiettivo è quello di sviluppare nuove strategie antitumorali bersagliando questo sovraccarico. Il progetto ridurrà l’accumulo di formiato attraverso la terapia genica e userà la melatonina per inibire la produzione di formiato.

Obiettivo

The key research goal of the MSCA PF is to enhance the leadership and research capability of the fellow Laura Martínez via implementing a multidisciplinary and innovative research project focused on targeting mitochondrial one-carbon metabolism and formate overflow to prevent the pro-invasive effect induced by this metabolite. The understanding of the specific metabolic dependencies involved in the metastatic cascade remains a challenging endeavor in cancer therapy since metastasis is the most common cause of death in cancer patients. In this sense, in the receiving group it has been recently demonstrated that mitochondrial one-carbon (1C) metabolism, which leads to formate overflow, plays a pivotal growth-independent role in promoting tumor cell invasiveness. However, effective strategies targeting this mitochondrial pathway have not yet been elucidated. Consequently, this proposal aims to further explore the promising role of 1C metabolism in cancer progression with the final goal to establish new strategies targeting formate overflow, potentially paving the way for the development of new anti-cancer therapies. The specific objectives are (1) preventing formate accumulation inducing formate degradation by gene-therapy approaches and (2) using melatonin as a therapeutic agent to inhibit formate production. This project will be carried out at Luxembourg Institute of Health and supervised by Dr. Johannes Meiser, a recognized expert in Cancer Metabolism. The experience of the applicant in melatonin and gene-therapy research, together with the recognized expertise of the host group in metabolomic will lead to the proper project achievement. This MSCA PF will provide the applicant with advanced technical training in metabolomic, the core expertise of the host lab, and cytometry, as well as self-reliant project management, leadership and mentoring skills, increasing Laura future opportunities towards becoming an autonomous researcher specialized on Cancer Metabolism.