A new drug that shows robust anti-tumour activity in a preclinical mouse model of cancer, is reported in this week’s Nature. The molecule, called MLN4924, is currently being evaluated in several phase I clinical trials.
MLN4924 suppresses the growth of human cancer cells that have been transplanted into mice, Teresa Soucy and colleagues report. It works by blocking an upstream step in a major intracellular pathway that regulates protein degradation. Another inhibitor of the pathway that targets the proteasome, bortezomib (Velcade), is already in clinical use for certain types of blood cancer. Bortezomib works by inhibiting a downstream step in the same pathway, so MLN4924 may have different clinical potential.
The new molecule also works by a different mechanism. It deregulates the part of the cell cycle, called S-phase, where DNA synthesis occurs. This results in DNA damage and the induction of programmed cell death or cancer cell ‘suicide’.