Detailseite
Projekt
Metabolische Therapieziele in zellulärer Seneszenz und post-seneszenten Tumoren - eine integrierte experimentell-bioinformatische Analyse
Antragsteller
Professor Dr. Eyal Gottlieb; Professor Dr. Clemens A. Schmitt
Fachliche Zuordnung
Hämatologie, Onkologie
Förderung
Förderung von 2016 bis 2024
Projektkennung
Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 282605471
A variety of failsafe programs protects the organism from oncogenic transformation and clinical tumor formation. One such program is the cessation of cell proliferation in response to severe cellular insults, termed cellular senescence (complementing apoptosis; i.e. programmed cell death). Senescence acts as a tumor-suppressive mechanism counteracting oncogenic action (oncogeneinduced senescence [OIS]). Many cancer therapeutics elicit an anti-proliferative effect by inducing senescence (therapy-induced senescence [TIS]), making this cellular state an important aspect of treatment response. Unlike apoptosis, senescent cells remain viable and are potentially dangerous, as they may promote inflammation as well as disease progression or relapse. We recently reported metabolic alterations in senescent cells as compared to their proliferating counterparts. The aim of this proposal is to identifysenescence-associated metabolic vulnerabilities that would allow us to eliminate senescent tumor cells towards improving long-term treatment outcome. We will utilize state-of-the-art analytical methods and computational metabolic simulations, using primary cells, genetically engineered mouse models and human cancer cell lines and tissues. This metabolic knowledge will be exploited to identify novel molecular targets, thus translating senescenceassociated metabolic alterations into conceptually novel therapeutic strategies in the clinic.
DFG-Verfahren
Deutsch-Israelische-Projektkooperationen
Internationaler Bezug
Israel
