The lecturers and professors of the Graduate Program in Cancer Biology invite Raul V. Duran to give a lecture in Bordeaux on Thursday, November 13, from 10:00 a.m. to 11:30 a.m. in the conference room of the BBS building, 2 rue du Dr Hoffmann Martinot.

Raul Duran will be available on Wednesday, November 12, during the morning, to talk with researchers who wish to meet him.
Contact: jose-eduardo.gomes@u-bordeaux.fr

Raul V. Duran
Spanish National Research Council (CSIC) – Séville
Group Leader of the Group of Metabolism and Cell Signaling

“Metabolic imbalance as a therapeutic strategy in cancer.”

 

Abstract

During last years, a great amount of effort has been dedicated to elucidate the crosstalk between cellular metabolic and bioenergetic flows with signaling processes, and how this interaction contributes to coordinate the growth and homeostasis of cells and tissues. Particularly, how these interaction mechanisms are deregulated in cancer at the molecular and cellular level is a matter of intense research, with the aim of using this knowledge to propose new therapeutic alternatives. Our research has established the processes of interaction between the metabolism of the amino acid glutamine, the most abundant in human blood and the most important from an energetic point of view for cells, with cell signaling via the mTOR pathway, a protein complex essential in the regulation of cell growth and metabolism, and autophagy. More recently, we focused our research on metabolic adaptation associated to therapy resistance in glioblastoma (GBM), one of the tumor types with the poorest survival outcomes. This work resulted in the identification of FGFR1 pathway as a major regulator of the signaling and metabolic rewiring associated with temozolomide (TMZ) resistance in GBM. Hence, we described a mechanism of resistance that operates at two major levels. First, a p53-mediated regulation of cell cycle inducing cell cycle arrest to allow DNA repair in response to TMZ. And second, a complete metabolic rewiring promoting lipid catabolism and preventing lipid peroxidation. Both the p53-mediated response and the metabolic adaptation are controlled by FGFR1, as inhibition of the FGFR1 pathway completely abolishes this signaling and metabolic reprograming, restoring sensitivity to TMZ. Our results also indicated a correlation of FGFR1 activity with poor prognosis in GBM patients, and validated the treatment of TMZ in combination with FGFR1 inhibitors as an efficient strategy to induce tumor cell death in pre-clinical animal models. This data position the receptor FGFR1 as a very promising candidate for evaluation in future clinical approaches to limit the development of therapy resistance to TMZ in GBM patients.

 

Biosketch

I obtained my PhD in Biochemistry at the University of Seville (Spain) in 2005 working on cellular bioenergetics. Then, I joined the lab of Prof. Eyal Gottlieb at the Beatson Institute for Cancer Research (Glasgow, UK) as a postdoctoral researcher to extend my expertise on broader aspects of cancer metabolism. Later, I moved to the lab of Prof. Michael N. Hall at the Biozentrum (Switzerland) as a senior postdoc to study the de-regulation of cellular signaling during cancer. In 2013 I joined the Institut Européen de Chimie et Biologie (Pessac, France) as a Group Leader (INSERM, CR position), integrating my previous expertise to investigate the crosstalk between metabolism and cell signaling in cancer cells. In 2018 I moved my lab to the Centro Andaluz de Biología Molecular y Medicina Regenerativa – CABIMER, upon my assignment as Senior Research Associate (Científico Titular) at CSIC. Since them, I am the Group Leader of the Group of Metabolism and Cell Signaling, and in the period 2019-2022 I was the Director of the Department of Dynamics and Cell Signaling at CABIMER. In the period 2020-2024 I was the Deputy Director of CABIMER. Currently, I am a member of the Executive Committee of the CONEXION CANCER-CSIC, and I serve as Associate Editor of the journal Cancer & Metabolism. Since January 2025 I serve as permanent evaluator (Gestor) of the Spanish Agency of Investigation (AEI), in the Biomedicine – Cancer commission.