Project Details
Projekt
An integrated experimental-computational investigation of metabolic vulnerabilities in cellular senescence and post-senescent cancers
Subject Area
Hematology, Oncology
Term
from 2016 to 2024
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 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 identify senescence-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 Programme
DIP Programme
International Connection
Israel
