Using metabolomics to monitor anticancer drugs.

Abstract

The metabolome of a cancer cell is likely to show changes after responding to an anticancer drug. These changes could be used to decide whether to continue treatment or, in the context of a drug trial, to indicate whether the drug is working and perhaps its mechanism of action. (Nuclear) magnetic resonance spectroscopy (NMR/MRS) methods can offer important insights into novel anticancer agents in order to accelerate the drug development process including time-course studies on the effect of a drug on its site of action (termed pharmacodynamics), in this case the cancer. In addition, some classes of anticancer agents currently under development (e.g. antiangiogenics) are designed to be used in combination with other drugs and will not cause tumour shrinkage when used as single agents in Phase 1 clinical trials. Thus NMR/MRS may have a special role in monitoring the pharmacodynamic actions of such drugs in early-phase clinical trials. This review focuses on the use of ex vivo NMR and in vivo MRS methods for monitoring the effect of some novel anticancer drugs on the cancer metabolome. Ex vivo NMR methods are complementary to in vivo measurements, as they can provide additional information and help in the interpretation of the in vivo data.