Fundamental Research Division
The DRF at the CEA assemble approximately 6,000 scientists since January 2016.
Scientific result | Cancer | DNA
The collaboration between American laboratories and a team from the CEA-IRCM has shown in vitro that inhibitors of the enzyme ATR specifically kill the cells of certain types of cancer.
In order to proliferate indefinitely, cancer cells must protect the integrity of their telomeres, the chromosomal extremities that, under normal circumstances, shorten at each division. In the majority of cancers, an enzyme called telomerase ensures this perpetual renewal. Nevertheless, this enzyme is absent from many glioblastomas and osteosarcomas. Another mechanism, based on the homologous recombination between chromosomes, intervenes to lengthen the telomeres. Could this phenomenon, known as ALT1, represent a target for anti-cancer agents?
To find out more, a Franco-American team2 involving the CEA-IRCM explored in vitro the cascade of molecular events that takes place in the ALT mechanism. Among the proteins concerned, an enzyme that regulates chromosomal recombination, named ATR, was shown to be essential to this phenomenon. Indeed, its specific inhibition by RNA interference or by a chemical compound named VE821 blocks the ALT mechanism.
The researchers then tested the effect of VE821 on the survival of different osteosarcoma and glioblastoma cell lines positive for telomerase activity or ALT, and on healthy cells. Their result shows that VE821 triggers apoptosis (i.e. cell death) selectively on ALT-positive cells. The same applies to another inhibitor of this enzyme. Cancerous cells using homologous recombination therefore appear to be hypersensitive to inhibitors of ATR, which could be a possible therapeutic approach. The next step is to test these compounds in vivo in a rodent glioma model that the team has recently developed.
Alternative lengthening of telomeres renders cancer cells hypersensitive to ATR inhibitors | Science
CEA is a French government-funded technological research organisation in four main areas: low-carbon energies, defense and security, information technologies and health technologies. A prominent player in the European Research Area, it is involved in setting up collaborative projects with many partners around the world.