Combinatorial nanotherapeutics: rewiring, then killing, cancer cells

Tumors are inherently resilient and often develop resistance against cancer therapies, leading to poor patient outcomes. With the sophisticated analytical and computational tools now available, much has been revealed about how molecularly targeted drugs affect the biochemical networks of cancer cells, enabling the directed design of treatment regimens that can better thwart resistance. In this issue of Science Signaling, Morton et al. demonstrate a nanoparticle system capable of sequentially delivering two drugs: The first inhibits an oncogenic pathway to sensitize the cells to DNA damage-induced apoptosis; the second is a genotoxic drug that takes advantage of the vulnerable state of the cancer cells to kill them with enhanced efficiency.