Anti-cancer treatments are often characterized by a familiar progression: at first tumors respond to a treatment, but cancer recurrence follows as tumor cells adapt to the therapy and resume unchecked growth. This adaptation of the tumor cells is frequently driven by epigenetic mechanisms to inactivate genes corresponding to the target of the therapy and enhance the expression of genes that promote resistance. Tumor cells that adopt these epigenetic defences can survive and multiply, meaning that the next generation of tumor cells will also be adapted to resist treatment.
BET proteins control the expression of several genes involved in the resistance to various anti-cancer treatments. BET inhibitors offer a unique opportunity to directly target resistance mechanisms and re-sensitize tumors to anti-cancer therapies. In essence, BET inhibitors can block the paths most used by tumor cells to evade treatment. These synergistic combinations of BET inhibitors with other drugs may improve efficacy through increased response rates and prolonged durability of responses. Zenith is focused on the clinical development of ZEN-3694 in combination with selected therapies to take advantage of BET inhibitors’ unique capability to combat treatment-resistant cancers.
