Rene Bernards of the Netherlands Cancer Institute has been
awarded an ERC Advanced Grant to conduct research into
senescence therapy for cancer as a strategy to overcome drug
The European Research Council Advanced Grant is allocated
annually to established, leading principal investigators who want
long-term funding to pursue a ground-breaking, high-risk project.
Advanced Grants may be awarded up to € 2.5 million for a period of
Systemic treatment of advanced cancers is hampered by the
development of drug resistance. To prevent resistance, Bernards'
laboratory has in the past used functional genetic screens to
discover several "synthetic lethal" drug combination therapies.
This has resulted in 8 clinical trials to date, including one
global phase 3 study.
In this program, he proposes a new approach to the treatment of
cancer, which is not based on combinations of drugs, but rather on
the sequential treatment with drugs. In a first treatment step,
cells will not only be induced to stop dividing, but they will at
the same time acquire a major new vulnerability that is
subsequently targeted with a second drug that selectively kills
cells having the newly acquired vulnerability.
Triggering a senescence response in cancer cells
To accomplish this, the Bernards group will take advantage of
recent observations that the cellular senescence response is not
only a property of primary cells, but can also be triggered in
advanced cancers. Such senescent cells have dramatic changes in
gene expression, chromatin structure and metabolism that will
hopefully exploited for their selective eradication.