Bendamustine is a hybrid antimetabolite and alkylating agent offering new therapeutic options for the treatment of non-Hodgkin lymphomas

Bendamustine is a rationally designed drug to combine both alkylating and antimetabolite functions with good tolerability. The cytotoxic effects of bendamustine differ from those of other alkylating agents, since in contrast to other alkylating agents, bendamustine activates a base excision DNA repair pathway rather than an alkyltransferase repair mechanism. Gene expression analyses showed that bendamustine has multiple mechanisms of action, including activation of DNA-damage stress responses and apoptosis, inhibition of mitotic checkpoints, and induction of mitotic catastrophe, a necrotic form of cell death that occurs during metaphase and is distinct from apoptosis (Leoni et al, Clin Cancer Res 2008).