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.
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.